scholarly journals Osteoclasts in Tumor Biology: Metastasis and Epithelial-Mesenchymal-Myeloid Transition

2021 ◽  
Vol 27 ◽  
Author(s):  
Kemal Behzatoglu
Keyword(s):  
Cancer Cells ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Tumor Biology ◽  
Active Role ◽  
Bone Modeling ◽  
Mesenchymal Transition ◽  
Local Spread ◽  
Metastatic Cancer Cells

Osteoclast is a specialized cell that originates from monocytic lineage, communicates closely with osteoblasts under physiological conditions, participates in bone modeling and re-modeling, contributes to calcium homeostasis and osteoimmunity. In pathological conditions, it is involved in many tumors such as giant cell bone tumor (osteoclastoma), aneurysmal bone cyst, osteosarcoma, and metastatic cancers, and it usually causes local spread and progression of the tumor, working against the host. Since osteoclasts play an active role in primary bone tumors and bone metastases, the use of anti-osteoclastic agents significantly reduces the mortality and morbidity rates of patients by preventing the progression and local spread of tumors. Osteoclasts also accompany undifferentiated carcinomas of many organs, especially pancreas, thyroid, bladder and ovary. Undifferentiated carcinomas rich in osteoclasts have osteoclastoma-like histology. In these organs, osteoclastoma-like histology may accompany epithelial carcinomas, and de novo, benign and borderline tumors. Mature and immature myeloid cells, including osteoclasts, play an active role in the tumor progression in primary and metastatic tumor microenvironment, in epithelial-mesenchymal transition (EMT), mesenchymal-epithelial-transition (MET), and cancer stem cell formation. Additionally, they are the most suitable candidates for cancer cells in cell fusion due to their evolutionary fusion capabilities. Myeloid features and markers (CD163, CD33, CD68 etc.) can be seen in metastatic cancer cells. Consequently, they provide metastatic cancer cells with motility, margination, transmigration, chemotaxis, phagocytosis, angiogenesis, matrix degradation, and resistance to chemotherapy. For these reasons, we think that the concept of Epithelial-Mesencyhmal-Myeloid-Transition (EMMT) will be more accurate than EMT for cancer cells with myeloid properties.

scholarly journals High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma

Oncogene ◽  
2020 ◽  
Vol 39 (42) ◽  
pp. 6529-6543 ◽  
Author(s):  
Beng Yang ◽  
Xiaode Feng ◽  
Hua Liu ◽  
Rongliang Tong ◽  
Jingbang Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Critical Role ◽  
Disease Free Survival ◽  
Mesenchymal Transition ◽  
Hcc Cells ◽  
Metastatic Cancer Cells

Abstract Exosomes play an important role in intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). However, cellular communication between heterogeneous HCC cells with different metastatic potentials and the resultant cancer progression are not fully understood in HCC. Here, HCC cells with high-metastatic capacity (97hm and Huhm) were constructed by continually exerting selective pressure on primary HCC cells (MHCC-97H and Huh7). Through performing exosomal miRNA sequencing in HCC cells with different metastatic potentials (MHCC-97H and 97hm), many significantly different miRNA candidates were found. Among these miRNAs, miR-92a-3p was the most abundant miRNA in the exosomes of highly metastatic HCC cells. Exosomal miR92a-3p was also found enriched in the plasma of HCC patient-derived xenograft mice (PDX) model with high-metastatic potential. Exosomal miR-92a-3p promotes epithelial-mesenchymal transition (EMT) in recipient cancer cells via targeting PTEN and regulating its downstream Akt/Snail signaling. Furthermore, through mRNA sequencing in HCC cells with different metastatic potentials and predicting potential transcription factors of miR92a-3p, upregulated transcript factors E2F1 and c-Myc were found in high-metastatic HCC cells promote the expression of cellular and exosomal miR-92a-3p in HCC by directly binding the promoter of its host gene, miR17HG. Clinical data showed that a high plasma exosomal miR92a-3p level was correlated with shortened overall survival and disease-free survival, indicating poor prognosis in HCC patients. In conclusion, hepatoma-derived exosomal miR92a-3p plays a critical role in the EMT progression and promoting metastasis by inhibiting PTEN and activating Akt/Snail signaling. Exosomal miR92a-3p is a potential predictive biomarker for HCC metastasis, and this may provoke the development of novel therapeutic and preventing strategies against metastasis of HCC.

scholarly journals Pseudopodial Actin Dynamics Control Epithelial-Mesenchymal Transition in Metastatic Cancer Cells

2010 ◽  
Vol 70 (9) ◽  
pp. 3780-3790 ◽  
Author(s):  
Jay Shankar ◽  
Anat Messenberg ◽  
Jackie Chan ◽  
T. Michael Underhill ◽  
Leonard J. Foster ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Actin Dynamics ◽  
Mesenchymal Transition ◽  
Metastatic Cancer Cells

The CXCL12-CXCR4 Signaling Axis Plays a Key Role in Cancer Metastasis and is a Potential Target for Developing Novel Therapeutics against Metastatic Cancer

2020 ◽  
Vol 27 (33) ◽  
pp. 5543-5561 ◽  
Author(s):  
Ping Yang ◽  
Yae Hu ◽  
Quansheng Zhou
Keyword(s):  
Cancer Cells ◽  
Progenitor Cells ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Cancer Therapeutics ◽  
Mesenchymal Transition ◽  
Cxcr4 Signaling ◽  
Signaling Axis

Metastasis is the main cause of death in cancer patients; there is currently no effective treatment for cancer metastasis. This is primarily due to our insufficient understanding of the metastatic mechanisms in cancer. An increasing number of studies have shown that the C-X-C motif chemokine Ligand 12 (CXCL12) is overexpressed in various tissues and organs. It is a key niche factor that nurtures the pre-metastatic niches (tumorigenic soil) and recruits tumor cells (oncogenic “seeds”) to these niches, thereby fostering cancer cell aggression and metastatic capabilities. However, the C-X-C motif chemokine Receptor 4 (CXCR4) is aberrantly overexpressed in various cancer stem/progenitor cells and functions as a CXCL12 receptor. CXCL12 activates CXCR4 as well as multiple downstream multiple tumorigenic signaling pathways, promoting the expression of various oncogenes. Activation of the CXCL12-CXCR4 signaling axis promotes Epithelial-Mesenchymal Transition (EMT) and mobilization of cancer stem/progenitor cells to pre-metastatic niches. It also nurtures cancer cells with high motility, invasion, and dissemination phenotypes, thereby escalating multiple proximal or distal cancer metastasis; this results in poor patient prognosis. Based on this evidence, recent studies have explored either CXCL12- or CXCR4-targeted anti-cancer therapeutics and have achieved promising results in the preclinical trials. Further exploration of this new strategy and its potent therapeutics effect against metastatic cancer through the targeting of the CXCL12- CXCR4 signaling axis may lead to a novel therapy that can clean up the tumor microenvironment (“soil”) and kill the cancer cells, particularly the cancer stem/progenitor cells (“seeds”), in cancer patients. Ultimately, this approach has the potential to effectively treat metastatic cancer.

scholarly journals Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Aaron M. Muscarella ◽  
Wei Dai ◽  
Patrick G. Mitchell ◽  
Weijie Zhang ◽  
Hai Wang ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Metastatic Cancer ◽  
Disseminated Tumor Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Osteogenic Cells ◽  
Cellular Protrusion

Abstract Migration and invasion are key properties of metastatic cancer cells. These properties can be acquired through intrinsic reprogramming processes such as epithelial-mesenchymal transition. In this study, we discovered an alternative “migration-by-tethering” mechanism through which cancer cells gain the momentum to migrate by adhering to mesenchymal stem cells or osteoblasts. This tethering is mediated by both heterotypic adherens junctions and gap junctions, and leads to a unique cellular protrusion supported by cofilin-coated actin filaments. Inhibition of gap junctions or depletion of cofilin reduces migration-by-tethering. We observed evidence of these protrusions in bone segments harboring experimental and spontaneous bone metastasis in animal models. These data exemplify how cancer cells may acquire migratory ability without intrinsic reprogramming. Furthermore, given the important roles of osteogenic cells in early-stage bone colonization, our observations raise the possibility that migration-by-tethering may drive the relocation of disseminated tumor cells between different niches in the bone microenvironment.

scholarly journals Vimentin on the move: new developments in cell migration

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1796 ◽  
Author(s):  
Rachel A. Battaglia ◽  
Samed Delic ◽  
Harald Herrmann ◽  
Natasha T. Snider
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cell Biology ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Building Blocks ◽  
Mesenchymal Transition ◽  
New Findings

The vimentin gene (VIM) encodes one of the 71 human intermediate filament (IF) proteins, which are the building blocks of highly ordered, dynamic, and cell type-specific fiber networks. Vimentin is a multi-functional 466 amino acid protein with a high degree of evolutionary conservation among vertebrates. Vim−/− mice, though viable, exhibit systemic defects related to development and wound repair, which may have implications for understanding human disease pathogenesis. Vimentin IFs are required for the plasticity of mesenchymal cells under normal physiological conditions and for the migration of cancer cells that have undergone epithelial–mesenchymal transition. Although it was observed years ago that vimentin promotes cell migration, the molecular mechanisms were not completely understood. Recent advances in microscopic techniques, combined with computational image analysis, have helped illuminate vimentin dynamics and function in migrating cells on a precise scale. This review includes a brief historical account of early studies that unveiled vimentin as a unique component of the cell cytoskeleton followed by an overview of the physiological vimentin functions documented in studies on Vim−/− mice. The primary focus of the discussion is on novel mechanisms related to how vimentin coordinates cell migration. The current hypothesis is that vimentin promotes cell migration by integrating mechanical input from the environment and modulating the dynamics of microtubules and the actomyosin network. These new findings undoubtedly will open up multiple avenues to study the broader function of vimentin and other IF proteins in cell biology and will lead to critical insights into the relevance of different vimentin levels for the invasive behaviors of metastatic cancer cells.

scholarly journals A Ca2+-ATPase Regulates E-cadherin Biogenesis and Epithelial-Mesenchymal Transition in Breast Cancer Cells

2018 ◽  
Author(s):  
Donna K. Dang ◽  
Monish Ram Makena ◽  
José P. Llongueras ◽  
Hari Prasad ◽  
Myungjun Ko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Benign Tumors ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractProgression of benign tumors to invasive, metastatic cancer is accompanied by the epithelial to mesenchymal transition (EMT), characterized by loss of the cell-adhesion protein E-cadherin. Although silencing mutations and transcriptional repression of the E-cadherin gene have been widely studied, not much is known about post-translational regulation of E-cadherin in tumors. We show that E-cadherin is tightly co-expressed with the secretory pathway Ca2+-ATPase isoform 2, SPCA2 (ATP2C2), in breast tumors. Loss of SPCA2 impairs surface expression of E-cadherin and elicits mesenchymal gene expression through disruption of cell adhesion in tumorspheres and downstream Hippo-YAP signaling. Conversely, ectopic expression of SPCA2 in triple negative breast cancer (TNBC) elevates baseline Ca2+ and YAP phosphorylation, enhances post-translational expression of E-cadherin, and suppresses mesenchymal gene expression. Thus, loss of SPCA2 phenocopies loss of E-cadherin in the Hippo signaling pathway and EMT-MET transitions, consistent with a functional role for SPCA2 in E-cadherin biogenesis. Furthermore, we show that SPCA2 suppresses invasive phenotypes, including cell migration in vitro and tumor metastasis in vivo. Based on these findings, we propose that SPCA2 functions as a key regulator of EMT and may be a potential therapeutic target for treatment of metastatic cancer.ImplicationsPost-translational control of E-cadherin and the Hippo pathway by calcium signaling regulates epithelial mesenchymal transition in breast cancer cells.

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