scholarly journals Mechanisms, Diagnosis and Treatment of Bone Metastases

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2944
Author(s):  
Jozef Ban ◽  
Valerie Fock ◽  
Dave N. T. Aryee ◽  
Heinrich Kovar
Keyword(s):  
Bone Marrow ◽  
Bone Metastases ◽  
Tumor Cells ◽  
Metastatic Tumor ◽  
Disease Outcome ◽  
Bone Marrow Niche ◽  
Therapeutic Implications ◽  
Metastatic Process ◽  
Breast And Prostate Cancer ◽  
Metastatic Sites

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, well-tolerated and more successful treatments for a significant improvement of patients’ quality of life and disease outcome. In this review, we provide comparative mechanistic insights into the bone metastatic process of various solid tumors, including pediatric cancers. We also highlight current and innovative approaches to biologically targeted therapy and immunotherapy. In particular, we discuss the role of the bone marrow microenvironment in the attraction, homing, dormancy and outgrowth of metastatic tumor cells and the ensuing therapeutic implications. Multiple signaling pathways have been described to contribute to metastatic spread to the bone of specific cancer entities, with most knowledge derived from the study of breast and prostate cancer. However, it is likely that similar mechanisms are involved in different types of cancer, including multiple myeloma, primary bone sarcomas and neuroblastoma. The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.

scholarly journals Detection of PIK3CA Mutations in Breast Cancer Bone Metastases

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8
Author(s):  
Manijeh Daneshmand ◽  
Jennifer E. L. Hanson ◽  
Mitra Nabavi ◽  
John F. Hilton ◽  
Lisa Vandermeer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastases ◽  
Cancer Cells ◽  
Primary Tumour ◽  
Breast Cancer Patients ◽  
Ct Guided ◽  
Mutation Status ◽  
Bone Biopsies ◽  
Metastatic Sites

Background. An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients. However, whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites. Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors, but their presence in breast cancer bone metastases has not been assessed previously. Results. Fourteen patients with breast cancer bone metastases were biopsied by three methods: CT-guided bone biopsies; bone marrow trephine biopsies; and bone marrow aspiration. Samples that were positive for cancer cells were obtained from six patients. Three of these patients had detectable PIK3CA mutations in bone marrow cancer cells. Primary tumor samples were available for four of the six patients assessed for PIK3CA status in their bone metastases. For each of these, the PIK3CA mutation status was the same in the primary and metastatic sites. Conclusions. PIK3CA mutations occur frequently in breast cancer bone metastases. The PIK3CA mutation status in bone metastases samples appears to reflect the PIK3CA mutation status in the primary tumour. Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors.

scholarly journals Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Shenglong Li ◽  
Wei Wang
Keyword(s):  
Bone Metastasis ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Bone Cells ◽  
Membrane Vesicles ◽  
Metastatic Tumor ◽  
Cell Types ◽  
Biological Phenomena ◽  
Breast And Prostate Cancer ◽  
Metastatic Sites

As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15–20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transporting intracellular substances. Recent studies have implicated EVs in the development of cancer. However, the potential roles of EVs in the pathological exchange of bone cells between tumors and the bone microenvironment remain an emerging area. This review is focused on the role of tumor-derived EVs in bone metastasis and possible regulatory mechanisms.

scholarly journals M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer

2020 ◽  
Vol 8 (2) ◽  
pp. e000979 ◽  
Author(s):  
Michal Hensler ◽  
Lenka Kasikova ◽  
Karel Fiser ◽  
Jana Rakova ◽  
Petr Skapa ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Patient Survival ◽  
Metastatic Tumor ◽  
Disease Outcome ◽  
Cytokine Signaling ◽  
Matrix Remodeling ◽  
Immune Effector ◽  
Effector Cells ◽  
Metastatic Sites

BackgroundThe immunological microenvironment of primary high-grade serous carcinomas (HGSCs) has a major impact on disease outcome. Conversely, little is known on the microenvironment of metastatic HGSCs and its potential influence on patient survival. Here, we explore the clinical relevance of the immunological configuration of HGSC metastases.MethodsRNA sequencing was employed on 24 paired primary tumor microenvironment (P-TME) and metastatic tumor microenvironment (M-TME) chemotherapy-naive HGSC samples. Immunohistochemistry was used to evaluate infiltration by CD8+ T cells, CD20+ B cells, DC-LAMP+ (lysosomal-associated membrane protein 3) dendritic cells (DCs), NKp46+ (natural killer) cells and CD68+CD163+ M2-like tumor-associated macrophages (TAMs), abundance of PD-1+ (programmed cell death 1), LAG-3+ (lymphocyte-activating gene 3) cells, and PD-L1 (programmed death ligand 1) expression in 80 samples. Flow cytometry was used for functional assessments on freshly resected HGSC samples.Results1468 genes were differentially expressed in the P-TME versus M-TME of HGSCs, the latter displaying signatures of extracellular matrix remodeling and immune infiltration. M-TME infiltration by immune effector cells had little impact on patient survival. Accordingly, M-TME-infiltrating T cells were functionally impaired, but not upon checkpoint activation. Conversely, cytokine signaling in favor of M2-like TAMs activity appeared to underlie inhibited immunity in the M-TME and poor disease outcome.ConclusionsImmunosuppressive M2-like TAM infiltrating metastatic sites limit clinically relevant immune responses against HGSCs.

Factors regulating the growth of metastatic cancer in bone.

1999 ◽  
pp. 333-347 ◽  
Author(s):  
B F Boyce ◽  
T Yoneda ◽  
T A Guise
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Bone Cells ◽  
Vascular Endothelial Cells ◽  
Current Knowledge ◽  
Metastatic Cancer ◽  
Bone Matrix ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Surface Proteins

Metastatic tumor cells can interfere directly with the function of bone cells involved in normal bone remodeling or indirectly by influencing the behavior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tumor cells interact closely with vascular endothelial cells, basement membrane and bone marrow stromal cells through cell surface proteins or by releasing factors which affect the function of these cells. Bidirectional interaction between marrow cells and tumor cells can give the latter a selective advantage for growth in bone which can lead to the destruction of or to increased production of bone matrix. Understanding of the mechanisms involved in tumor metastasis and growth in bone has increased in recent years, and in this review we shall describe current knowledge of these mechanisms and of the predilection of certain types of cancers to metastasize to bone, their growth in the bone microenvironment and interactions between them and bone cells. Because metastatic breast cancer has been studied more than any other, we shall focus on it as a representative example, although the general principles apply to other types of cancer and to myeloma.

scholarly journals Bone Marrow Adipocytes: A Link between Obesity and Bone Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 364
Author(s):  
Michaela R. Reagan ◽  
Heather Fairfield ◽  
Clifford J. Rosen
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Bone Cancer ◽  
Research Field ◽  
Bone Marrow Niche ◽  
Open Research ◽  
Bone Marrow Adipocytes ◽  
Cancer Initiation ◽  
New Ideas ◽  
Research Questions

Cancers that grow in the bone marrow are for most patients scary, painful, and incurable. These cancers are especially hard to treat due to the supportive microenvironment provided by the bone marrow niche in which they reside. New therapies designed to target tumor cells have extended the life expectancy for these patients, but better therapies are needed and new ideas for how to target these cancers are crucial. This need has led researchers to interrogate whether bone marrow adipocytes (BMAds), which increase in number and size during aging and in obesity, contribute to cancer initiation or progression within the bone marrow. Across the globe, the consensus in the field is a unified “yes”. However, how to target these adipocytes or the factors they produce and how BMAds interact with different tumor cells are open research questions. Herein, we review this research field, with the goal of accelerating research in the network of laboratories working in this area and attracting bright scientists with new perspectives and ideas to the field in order to bring about better therapies for patients with bone cancers.

scholarly journals Dissecting the Role of Bone Marrow Stromal Cells on Bone Metastases

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Denise Buenrostro ◽  
Serk In Park ◽  
Julie A. Sterling
Keyword(s):  
Bone Marrow ◽  
Bone Metastases ◽  
Tumor Cells ◽  
Bone Marrow Cells ◽  
Current Knowledge ◽  
Metastatic Cancer ◽  
Cell Types ◽  
Bone Microenvironment ◽  
Or Gene ◽  
Different Cell Types

Tumor-induced bone disease is a dynamic process that involves interactions with many cell types. Once metastatic cancer cells reach the bone, they are in contact with many different cell types that are present in the cell-rich bone marrow. These cells include the immune cells, myeloid cells, fibroblasts, osteoblasts, osteoclasts, and mesenchymal stem cells. Each of these cell populations can influence the behavior or gene expression of both the tumor cells and the bone microenvironment. Additionally, the tumor itself can alter the behavior of these bone marrow cells which further alters both the microenvironment and the tumor cells. While many groups focus on studying these interactions, much remains unknown. A better understanding of the interactions between the tumor cells and the bone microenvironment will improve our knowledge on how tumors establish in bone and may lead to improvements in diagnosing and treating bone metastases. This review details our current knowledge on the interactions between tumor cells that reside in bone and their microenvironment.

scholarly journals Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4310
Author(s):  
Ahmad Othman ◽  
Marcus Winogradzki ◽  
Linus Lee ◽  
Manish Tandon ◽  
Alan Blank ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Bone Microenvironment ◽  
Aberrant Expression ◽  
Parathyroid Hormone Related Protein ◽  
Metastatic Process

Bone metastasis is a frequent complication of breast cancer with nearly 70% of metastatic breast cancer patients developing bone metastasis during the course of their disease. The bone represents a dynamic microenvironment which provides a fertile soil for disseminated tumor cells, however, the mechanisms which regulate the interactions between a metastatic tumor and the bone microenvironment remain poorly understood. Recent studies indicate that during the metastatic process a bidirectional relationship between metastatic tumor cells and the bone microenvironment begins to develop. Metastatic cells display aberrant expression of genes typically reserved for skeletal development and alter the activity of resident cells within the bone microenvironment to promote tumor development, resulting in the severe bone loss. While transcriptional regulation of the metastatic process has been well established, recent findings from our and other research groups highlight the role of the autophagy and secretory pathways in interactions between resident and tumor cells during bone metastatic tumor growth. These reports show high levels of autophagy-related markers, regulatory factors of the autophagy pathway, and autophagy-mediated secretion of matrix metalloproteinases (MMP’s), receptor activator of nuclear factor kappa B ligand (RANKL), parathyroid hormone related protein (PTHrP), as well as WNT5A in bone metastatic breast cancer cells. In this review, we discuss the recently elucidated mechanisms and their crosstalk with signaling pathways, and potential therapeutic targets for bone metastatic disease.

Sign in / Sign up

Export Citation Format

Share Document