Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

Abstract

Background/Aims: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63) and gastric cancer (SGC7901) cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

Exosomal miR-27a Derived from Gastric Cancer Cells Regulates the Transformation of Fibroblasts into Cancer-Associated Fibroblasts

“…The components of the tumor microenvironment may also affect patients survival [22]. It had already demonstrated that demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression [23]. Among the predominant factors in the tumor microenvironment, are fibroblasts that can be transformed into CAFs under certain conditions [24].…”

Enhancement of Anti-Leukemia Immunity by Leukemia–Derived Exosomes Via Downregulation of TGF-β1 Expression

“…As shown in Fig. 1a under electron microscopy, LEX TGF-β1si was a population of micro-vesicles with 40-100 nm in diameter and was consistent with the typical morphology of exosomes [24]. To determine whether knockdown of TGF-β1 expression in L1210 cells could effectively affect the protein pattern on an exosomal level or not, Western blot analysis was performed.…”

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

“…Previous studies identified that exosomes could promote the proliferation and migration of gastric cancer cells via the phosphatidylinositol-3 kinase/Akt, nuclear factor-κB and Hedgehog signaling pathways (11)(12)(13). Through this exosomal regulation, gastric cancer cells may become more prone to invade the serosa and exfoliate into the cavity with increased proliferative and migratory abilities.…”

“…Wang et al (48) suggested that serum exosomal miR-19b-3p and miR-106a-5p were novel potential biomarkers for the detection of gastric cancer. Tokuhisa et al (49) suggested that exosomal miR-21 and miR-1225-5p from peritoneal lavage fluid were upregulated in the later stages of gastric cancer and correlated with serosal invasion, which could potentially predict peritoneal recurrence following curative gastric cancer resection (50). However, it remains unknown whether exosomal miRNAs from serum or peritoneum lavage fluid have adequate sensitivity or specificity to serve as novel tumor makers.…”