Tumor activated platelets induce vascular mimicry in mesenchymal stem cells and aid metastasis

肿瘤激活的血小板诱导间充质干细胞血管模拟并促进转移

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作者:Avishek Bhuniya, Anirban Sarkar, Aishwarya Guha, Pritha Roy Choudhury, Saurav Bera, Jasmine Sultana, Mohona Chakravarti, Sukanya Dhar, Juhina Das, Ipsita Guha, Nilanjan Ganguly, Saptak Banerjee, Anamika Bose, Rathindranath Baral

Abstract

Extent of metastasis influences activation of platelets in tumor-microenvironment. Activated platelets potentiate mesenchymal-stem-cells (MSCs) to migrate in secondary metastatic sites without participation in process of invasion. Presence of higher percentage of MSCs along with activated-platelets induces formation of vascular-mimicry (VM). The pathophysiology, VM, has already been reported in multiple types of cancer including lung, ovary, melanoma etc. and related to poor-prognosis. Interaction of MSCs with platelets in cell-to-cell contact dependent manner is essential for their migration, thereby, VM. Evidences are obtained suggesting that under influence of tumor-associated-activated-platelets, expressions of vimentin, ve-cadherin are increased, along with decrease in e-cadherin on CD105+ MSCs in both mRNA and protein levels that may help in formation of vessel like structure in VM. Adoptive transfer of MSCs along with tumor-activated-platelets causes greater B16 melanoma metastasis at lungs in comparison to MSCs with non-activated platelets. Presence of CD105+Vimentin+ MSCs in vessel like structure in the metastatic lung confirms the involvement of platelet-activated-MSCs in VM, thereby, in metastasis.

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