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Fig. 7 | Molecular Cancer

Fig. 7

From: Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance

Fig. 7

Chemotherapy-promoting intercellular transfer of ABCB1 occurs in vivo and is associated with chemotherapeutic efficacy in cancer patients. A The nude mice models are established by subcutaneously injecting a mixture of GFP+ KB cells and ABCB1+ KBv200 cells at a ratio of 1:1. Confocol images show the intercellular transfer of ABCB1 in xenograft tumors. Blue represents DAPI and red represents Cy3-ABCB1. B The nude mice models are established as control by subcutaneously injecting pure GFP+ KB cells or ABCB1+ KBv200 cells. C The systemic transfer models are generated by subcutaneously injecting GFP+ KB cells and KBv200 cells into the contralateral armpit of forelimb, respectively. Confocol images show the intercellular transfer of ABCB1 in xenograft tumors. D-E The mean percentage of ABCB1+ KB cells in isolated KB xenograft tumors is found to be elevated in mice receiving the treatment with DDP, as compared to that in untreated mice, whether in local mice model (D) or in systemic mice model (E). F ABCB1 surface expression was determined in peripheral blood monocyte subpopulations from patients with NSCLC before and after they received the first chemotherapy. G-H Each bar means the fold change of ABCB1 expression for each patient before and after chemotherapy. The bars above the horizontal axis represent the increase of ABCB1 expression after patients underwent chemotherapy. Ten cases of patients were found a rapid increase in ABCB1 surface expression. I Occurrence of ABCB1 intercellular transfer in patients predicted a poor chemotherapeutic efficacy. J When the heterogeneous tumor suffers the chemotherapy, ABCB1-overexpressing donor cancer cells release more EVs containing ABCB1 via the upregulation of Rab8B, then recipient sensitive cells take up those ABCB1-incorporated EVs through a clathrin-mediated dynamin 2-dependent endocytic pathway, following by a Rab5-mediated recycling back to plasma membrane. Hence the sensitive cancer cells instantly acquire the “short-term” resistance for evading the cytotoxicity of chemotherapeutics

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