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MCF-7 Cell Derived Soluble Factors Define Growth of Vascular and Lymphatic Endothelial Cells: Modulatory Role of miR193a

ABSTRACT: Angiogenesis and Lymphangiogenesis plays a key role in promoting tumor growth and breast cancer progression as well as metastasis. Active angiogenic process within the tumor tissue is known to promote cancer/tumor growth via nutrient supply, moreover, soluble molecules secreted by lymphatic endothelial cells (ECs) promotes tumor growth. Hence is feasible that paracrine factors generated by breast cancer cells play a role in regulating tumor neovascularization by lymphatic and vascular ECs. Here using cultured VECs and LECs assessed the paracrine impact of MCF-7 breast cancer derived soluble factors on LEC and VEC growth (cell number), gene expression (micro array) and angiogenic proteins (protein array). Moreover, we explored the modulatory actions of miR193 on LEC and VEC growth driven by MCF-7 derived conditioned medium (MCF7-CM). We demonstrate that MCF7-CM differentially modulates VEC and LEC growth, i.e. induces VEC growth and inhibits LEC growth. Moreover, the growth actions of MCF7-CM were accompanied with differential modulation VEC and LEC growth regulatory genes, that were further altered by miR193 a pretreatment of MCF7 cells. Our findings provide in-depth analysis of MCF7-CM altered genes relevant for angiogenesis and lymphogenesis. The fact that vascular capillaries support growth and lymphatic capillaries play a role counteracting cancer growth (kill cancer cells), together with our observation in VECs and LECs, suggests that MCF-7 breast cancer cells differentially modulate vascular and lymphatic growth to facilitate their survival and growth. Since miR193a abrogates the effects of MCF7-CM, it may be an effective therapeutic tool against breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189084 | GEO | 2022/07/13

REPOSITORIES: GEO

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Project description:The subpopulations of mesenchymal stem cells isolated from breast adipose tissue which display migrated towards conditioned media from MDA-MB231 cell line were expanded for miRNA analysis. The tumor microenvironment (TM) is known to promote tumor growth and progression. Ubiquitously distributed tissue resident stem cells (MSCs) elicit regenerative properties. In addition, they are capable of homing to sites of inflammation, injury, and tumor. Considering the tumor tropic property of MSCs, the interaction between the breast cancer (BC) microenvironment and breast resident adipose tissue derived MSCs (ASCs) merits further investigations. Initial data indicate that a subset of ASCs derived from breast adipose tissue (B-ASCs) display a high affinity towards the conditioned media (CM) from two breast cancer cell lines, MDA-MB231 (MDA-CM) and MCF7 (MCF-CM). Profiling secreted cytokines of these CMs identified significant expression of angiogenin, GM-CSF, and IL-6. While the expression of GRO-α, MCP-1, RANTES, and IL-1α is more pronounced in MDA-CM, MCF-CM contains higher amounts of IGFBP2, TRAIL, and ErbB3. Gene expression profiling suggests that despite the distinct differences, both migratory subset of B-ASCs towards MDA-CM and MCF-CM display perturbed expression of genes like KISS1, TNSF1, IL18 and MMP2, which could be associated with a defensive role of B-ASCs. In addition, the BC microenvironment alters microRNA (miRNA) expressions in B-ASCs. in this study the migratory cells were evaluated for miRNA expression versus non-migratory counterparts. as controls unexposed parental cell lines (2) were used on the same hybridization chip in which one labeled Hy3 and other labeled Hy5. The ratio of the control parental cells was used as base nanalysis of miRNA expression in MSCs. we also include another control in this study, the migratory subpopulations of MSCs which display migratory potentials against protein gradient (M5) were analyzed for miRNA expression versus non-migratory counterparts (NM-5). using this control facilitate identification of those miRNA responsive to tumor CM. the data analysis confirm that altered gene and miRNA profiles resulted from exposure of MCF-CM and MDA-CM on B-ASCs are similar to those observed in B-ASCs isolated from breast adipose tissue of BC patients. Analysis the signaling between the B-ASCs and TM may help in understanding the possible role of B-ASCs in stasis, progression, or regression of the BC.

Project description:The subpopulations of mesenchymal stem cells isolated from breast adipose tissue which display migrated towards conditioned media from MDA-MB231 cell line were expanded for miRNA analysis. The tumor microenvironment (TM) is known to promote tumor growth and progression. Ubiquitously distributed tissue resident stem cells (MSCs) elicit regenerative properties. In addition, they are capable of homing to sites of inflammation, injury, and tumor. Considering the tumor tropic property of MSCs, the interaction between the breast cancer (BC) microenvironment and breast resident adipose tissue derived MSCs (ASCs) merits further investigations. Initial data indicate that a subset of ASCs derived from breast adipose tissue (B-ASCs) display a high affinity towards the conditioned media (CM) from two breast cancer cell lines, MDA-MB231 (MDA-CM) and MCF7 (MCF-CM). Profiling secreted cytokines of these CMs identified significant expression of angiogenin, GM-CSF, and IL-6. While the expression of GRO-M-NM-1, MCP-1, RANTES, and IL-1M-NM-1 is more pronounced in MDA-CM, MCF-CM contains higher amounts of IGFBP2, TRAIL, and ErbB3. Gene expression profiling suggests that despite the distinct differences, both migratory subset of B-ASCs towards MDA-CM and MCF-CM display perturbed expression of genes like KISS1, TNSF1, IL18 and MMP2, which could be associated with a defensive role of B-ASCs. In addition, the BC microenvironment alters microRNA (miRNA) expressions in B-ASCs. in this study the migratory cells were evaluated for miRNA expression versus non-migratory counterparts. as controls unexposed parental cell lines (2) were used on the same hybridization chip in which one labeled Hy3 and other labeled Hy5. The ratio of the control parental cells was used as base nanalysis of miRNA expression in MSCs. we also include another control in this study, the migratory subpopulations of MSCs which display migratory potentials against protein gradient (M5) were analyzed for miRNA expression versus non-migratory counterparts (NM-5). using this control facilitate identification of those miRNA responsive to tumor CM. the data analysis confirm that altered gene and miRNA profiles resulted from exposure of MCF-CM and MDA-CM on B-ASCs are similar to those observed in B-ASCs isolated from breast adipose tissue of BC patients. Analysis the signaling between the B-ASCs and TM may help in understanding the possible role of B-ASCs in stasis, progression, or regression of the BC. The microRNA expression of migratory subpopulations were compared to parental populations of MSCs.

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MCF-7 Cell Derived Soluble Factors Define Growth of Vascular and Lymphatic Endothelial Cells: Modulatory Role of miR193a

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