scholarly journals Mesenchymal Stem/Stromal Cells in Stromal Evolution and Cancer Progression

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca Cammarota ◽  
Mikko O. Laukkanen
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Cancer Biology ◽  
Tumor Stroma ◽  
Epithelial Cancer ◽  
Stromal Compartment ◽  
Hematopoietic Stem ◽  
Hematopoietic Malignancies ◽  
Total Body

The study of cancer biology has mainly focused on malignant epithelial cancer cells, although tumors also contain a stromal compartment, which is composed of stem cells, tumor-associated fibroblasts (TAFs), endothelial cells, immune cells, adipocytes, cytokines, and various types of macromolecules comprising the extracellular matrix (ECM). The tumor stroma develops gradually in response to the needs of epithelial cancer cells during malignant progression initiating from increased local vascular permeability and ending to remodeling of desmoplastic loosely vascularized stromal ECM. The constant bidirectional interaction of epithelial cancer cells with the surrounding microenvironment allows damaged stromal cell usage as a source of nutrients for cancer cells, maintains the stroma renewal thus resembling a wound that does not heal, and affects the characteristics of tumor mesenchymal stem/stromal cells (MSCs). Although MSCs have been shown to coordinate tumor cell growth, dormancy, migration, invasion, metastasis, and drug resistance, recently they have been successfully used in treatment of hematopoietic malignancies to enhance the effect of total body irradiation-hematopoietic stem cell transplantation therapy. Hence, targeting the stromal elements in combination with conventional chemotherapeutics and usage of MSCs to attenuate graft-versus-host disease may offer new strategies to overcome cancer treatment failure and relapse of the disease.

scholarly journals Targeting the Tumor Microenvironment for Cancer Therapy

2013 ◽  
Vol 59 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Nor Eddine Sounni ◽  
Agnès Noel
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Local Environment ◽  
Tumor Stroma ◽  
Host Cells ◽  
Stromal Compartment ◽  
Tumor Infiltrate ◽  
Cellular Components

BACKGROUND With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic. CONTENT The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix. SUMMARY A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix.

scholarly journals Activated fibroblasts enhance cancer cell migration by microvesicles-mediated transfer of Galectin-1

2021 ◽  
Author(s):  
Alessandra Toti ◽  
Alice Santi ◽  
Elisa Pardella ◽  
Ilaria Nesi ◽  
Richard Tomasini ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Tumor Stroma ◽  
Activation Process ◽  
Cancer Cell Migration ◽  
Stromal Compartment ◽  
Activated Fibroblasts

AbstractCancer-associated fibroblasts (CAFs) are one of the main components of the stromal compartment in the tumor microenvironment (TME) and the crosstalk between CAFs and cancer cells is essential for tumor progression and aggressiveness. Cancer cells mediate an activation process, converting normal fibroblasts into CAFs, that are characterized by modified expression of many proteins and increased production and release of microvesicles (MVs), extracellular vesicles generated by outwards budding from the cell membrane. Recent evidence underlined that the uptake of CAF-derived MVs changes the overall protein content of tumor cells. In this paper, we demonstrate that tumor activated fibroblasts overexpress Galectin-1 (Gal-1) and consequently release MVs containing increased levels of this protein. The uptake of Gal-1 enriched MVs by tumor cells leads to the upregulation of its intracellular concentration, that strongly affects cancer cell migration, while neither proliferation nor adhesion are altered. Accordingly, tumor cells co-cultured with fibroblasts silenced for Gal-1 have a reduced migratory ability. The present work reveals the key role of an exogenous protein, Gal-1, derived from activated fibroblasts, in cancer progression, and contributes to clarify the importance of MVs-mediated protein trafficking in regulating tumor-stroma crosstalk.

scholarly journals Mitochondria at Center of Exchanges between Cancer Cells and Cancer-Associated Fibroblasts during Tumor Progression

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3017
Author(s):  
Lisa Nocquet ◽  
Philippe P. Juin ◽  
Frédérique Souazé
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Tumor Stroma ◽  
Solid Cancer ◽  
Cancer Therapies ◽  
Cancer Associated Fibroblasts ◽  
Metabolic Functions ◽  
Mutational Status

Resistance of solid cancer cells to chemotherapies and targeted therapies is not only due to the mutational status of cancer cells but also to the concurring of stromal cells of the tumor ecosystem, such as immune cells, vasculature and cancer-associated fibroblasts (CAFs). The reciprocal education of cancer cells and CAFs favors tumor growth, survival and invasion. Mitochondrial function control, including the regulation of mitochondrial metabolism, oxidative stress and apoptotic stress are crucial for these different tumor progression steps. In this review, we focus on how CAFs participate in cancer progression by modulating cancer cells metabolic functions and mitochondrial apoptosis. We emphasize that mitochondria from CAFs influence their activation status and pro-tumoral effects. We thus advocate that understanding mitochondria-mediated tumor–stroma interactions provides the possibility to consider cancer therapies that improve current treatments by targeting these interactions or mitochondria directly in tumor and/or stromal cells.

scholarly journals Matrix Stiffness Modulates Metabolic Interaction between Human Stromal and Breast Cancer Cells to Stimulate Epithelial Motility

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 432
Author(s):  
Iván Ponce ◽  
Nelson Garrido ◽  
Nicolás Tobar ◽  
Francisco Melo ◽  
Patricio C. Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Resonance Energy ◽  
Metabolic Reprogramming ◽  
Dependent Manner ◽  
Functional Link

Breast tumors belong to the type of desmoplastic lesion in which a stiffer tissue structure is a determinant of breast cancer progression and constitutes a risk factor for breast cancer development. It has been proposed that cancer-associated stromal cells (responsible for this fibrotic phenomenon) are able to metabolize glucose via lactate production, which supports the catabolic metabolism of cancer cells. The aim of this work was to investigate the possible functional link between these two processes. To measure the effect of matrix rigidity on metabolic determinations, we used compliant elastic polyacrylamide gels as a substrate material, to which matrix molecules were covalently linked. We evaluated metabolite transport in stromal cells using two different FRET (Fluorescence Resonance Energy Transfer) nanosensors specific for glucose and lactate. Cell migration/invasion was evaluated using Transwell devices. We show that increased stiffness stimulates lactate production and glucose uptake by mammary fibroblasts. This response was correlated with the expression of stromal glucose transporter Glut1 and monocarboxylate transporters MCT4. Moreover, mammary stromal cells cultured on stiff matrices generated soluble factors that stimulated epithelial breast migration in a stiffness-dependent manner. Using a normal breast stromal cell line, we found that a stiffer extracellular matrix favors the acquisition mechanistical properties that promote metabolic reprograming and also constitute a stimulus for epithelial motility. This new knowledge will help us to better understand the complex relationship between fibrosis, metabolic reprogramming, and cancer malignancy.

scholarly journals Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 68
Author(s):  
Fulvio Massaro ◽  
Florent Corrillon ◽  
Basile Stamatopoulos ◽  
Nathalie Meuleman ◽  
Laurence Lagneaux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Communication ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Wide Range ◽  
Major Player

Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression.

scholarly journals P11.41 Comparison of fibroblast activation protein expression and localization in glioblastomas and brain metastases

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii52-iii52
Author(s):  
P Busek ◽  
M Zubal ◽  
B Chmielova ◽  
Z Vanickova ◽  
P Hrabal ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Brain Metastases ◽  
Cancer Cells ◽  
Brain Tissue ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Glioma Cells ◽  
Fibroblast Activation Protein ◽  
Epithelial Cancer ◽  
Fibroblast Activation

Abstract BACKGROUND Fibroblast activation protein (FAP) is a transmembrane serine protease that is frequently upregulated in the tumor microenvironment. In several cases, FAP protein itself and/or FAP expressing stromal cells have been shown to contribute to cancer progression and to be associated with more aggressive cancer behaviour and shorter patient survival. The aim of this study was to determine FAP expression in glioblastomas and brain metastases and to identify the cell types that express FAP in the microenvironment of these malignancies. MATERIAL AND METHODS FAP enzymatic activity and protein concentration were determined in samples from patients with brain metastases, glioblastomas and pharmacoresistant epilepsy (control non-tumorous brain tissue) by an enzymatic assay using a specific fluorogenic substrate and ELISA, respectively. Immunohistochemical labelling with antibodies against FAP and markers of astroglia, epithelial cancer cells and mesenchymal stromal cells was performed to characterize FAP expressing cells. RESULTS FAP was significantly upregulated in the majority of glioblastomas and brain metastases in comparison to non-tumorous brain tissue. In glioblastomas, FAP was localized perivascularly and in mesenchymal cells, and in part of the tumors also in the glioma cells. In brain metastases, FAP positivity was abundantly present in the stroma and predominantly co-localised with markers of mesenchymal stromal cells (TE-7, SMA, PDGFRbeta, NG2), but there was no overlap between FAP and markers of epithelial cancer cells (EpCAM, pancytokeratin). CONCLUSION FAP is upregulated in the microenvironment of human glioblastomas and brain metastases compared to non-tumorous brain tissue. In glioblastomas, FAP is expressed in part of the glioma cells, in pericytes and mesenchymal stromal cells, whereas no positivity in cancer cells and more abundant FAP+ stroma was detected in brain metastases. The selective expression of FAP in these brain tumors may be useful for the visualization and possibly therapeutic targeting of their tumor microenvironment. GRANT SUPPORT Ministry of Health of the Czech Republic, grant No. 15-31379A, Progres Q28/LF1, 2015064 LM EATRIS and the project,Center for Tumor Ecology - Research of the Cancer Microenvironment Supporting Cancer Growth and Spread” (reg. n. CZ.02.1.01/0.0/0.0/16_019/0000785) supported by the Operational Programme Research, Development and Education.

TOPOGRAPHY MEDIATED REGULATION OF HER-2 EXPRESSION IN BREAST CANCER CELLS

Nano LIFE ◽  
2012 ◽  
Vol 02 (03) ◽  
pp. 1241009 ◽  
Author(s):  
AMITA DAVEREY ◽  
AUSTIN C. MYTTY ◽  
SRIVATSAN KIDAMBI
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Tumor ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Her 2 ◽  
Micro Topography

This article demonstrates that the surface micro-topography regulates the biology of breast cancer cells, including the expression of HER-2 gene and protein. The breast tumor microenvironment is made up of heterogenous mixture of pores, ridges and collagen fibers with well defined topographical features. Although, significant progress has been achieved towards elucidating the biochemical and molecular mechanisms that underlie breast cancer progression, quantitative characterization of the associated mechanical/topographical properties and their role in breast tumor progression remains largely unexplored. Therefore, the aim of this study is to investigate the effect of topography on the adhesion and biology of breast cancer cells in in vitro cultures. Polydimethylsiloxane (PDMS) surfaces containing different topographies were coated with polyelectrolyte multilayers (PEMs) to improve cell adhesion and maintain cell culture. HER-2 expressing breast cancer cells, BT-474 and SKBr3, were cultured on these PDMS surfaces. We demonstrate that micro-topography affects the cell adhesion and distribution depending on the topography on the PDMS surfaces. We also report for the first time that surface topography down-regulates the HER-2 gene transcription and protein expression in breast cancer cells when cultured on PDMS surfaces with micro-topographies compared to the tissue culture polystyrene surface (TCPS) control. Results from this study indicate that micro-topography modulates morphology of cells, their distribution and expression of HER-2 gene and protein in breast cancer cells. This study provides a novel platform for studying the role of native topography in the progression of breast cancer and has immense potential for understanding the breast cancer biology.

scholarly journals Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression

Tumor Biology ◽  
2018 ◽  
Vol 40 (2) ◽  
pp. 101042831875620 ◽  
Author(s):  
Filipa Lopes-Coelho ◽  
Sofia Gouveia-Fernandes ◽  
Jacinta Serpa
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Inflammatory Cells ◽  
Metabolic Adaptation ◽  
Metabolic Cooperation ◽  
Metabolic Remodeling ◽  
Organ Tissue ◽  
Cancerous Cells

The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

scholarly journals Breast Cancer Cells in Microgravity: New Aspects for Cancer Research

2020 ◽  
Vol 21 (19) ◽  
pp. 7345 ◽  
Author(s):  
Mohamed Zakaria Nassef ◽  
Daniela Melnik ◽  
Sascha Kopp ◽  
Jayashree Sahana ◽  
Manfred Infanger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Tumor Model ◽  
Cancer Drug ◽  
Cancer Therapies

Breast cancer is the leading cause of cancer death in females. The incidence has risen dramatically during recent decades. Dismissed as an “unsolved problem of the last century”, breast cancer still represents a health burden with no effective solution identified so far. Microgravity (µg) research might be an unusual method to combat the disease, but cancer biologists decided to harness the power of µg as an exceptional method to increase efficacy and precision of future breast cancer therapies. Numerous studies have indicated that µg has a great impact on cancer cells; by influencing proliferation, survival, and migration, it shifts breast cancer cells toward a less aggressive phenotype. In addition, through the de novo generation of tumor spheroids, µg research provides a reliable in vitro 3D tumor model for preclinical cancer drug development and to study various processes of cancer progression. In summary, µg has become an important tool in understanding and influencing breast cancer biology.

scholarly journals Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 367 ◽  
Author(s):  
Melnik ◽  
Sahana ◽  
Corydon ◽  
Kopp ◽  
Nassef ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Signal Pathways ◽  
Dependent Manner ◽  
Spheroid Formation ◽  
Mesenchymal Transition

Detachment and the formation of spheroids under microgravity conditions can be observed with various types of intrinsically adherent human cells. In particular, for cancer cells this process mimics metastasis and may provide insights into cancer biology and progression that can be used to identify new drug/target combinations for future therapies. By using the synthetic glucocorticoid dexamethasone (DEX), we were able to suppress spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells that were exposed to altered gravity conditions on a random positioning machine. DEX inhibited the growth of three-dimensional cell aggregates in a dose-dependent manner. In the first approach, we analyzed the expression of several factors that are known to be involved in key processes of cancer progression such as autocrine signaling, proliferation, epithelial–mesenchymal transition, and anoikis. Wnt/β-catenin signaling and expression patterns of important genes in cancer cell growth and survival, which were further suggested to play a role in three-dimensional aggregation, such as NFKB2, VEGFA, CTGF, CAV1, BCL2(L1), or SNAI1, were clearly affected by DEX. Our data suggest the presence of a more complex regulation network of tumor spheroid formation involving additional signal pathways or individual key players that are also influenced by DEX.

Sign in / Sign up

Export Citation Format

Share Document