Abstract

The complex cross-talk between tumor cells and their surrounding stromal environment plays a key role in the pathogenesis of cancer. Among several cell types that constitute the tumor stroma, bone marrow-derived mesenchymal stem cells (BM-MSCs) selectively migrate toward the tumor microenvironment and contribute to the active formation of tumor-associated stroma. Therefore, here we elucidate the involvement of BM-MSCs to promote osteosarcoma (OS) and hepatocellular carcinoma (HCC) cells migration and invasion and deepening the role of specific pathways. We analyzed the function of aquaporin 1 (AQP1), a water channel known to promote metastasis and neoangiogenes. AQP1 protein levels were analyzed in OS (U2OS) and HCC (SNU-398) cells exposed to conditioned medium from BM-MSCs. Tumor cell migration and invasion in response to BM-MSC conditioned medium were evaluated through a wound healing assay and Boyden chamber, respectively. The results showed that the AQP1 level was increased in both tumor cell lines after treatment with BM-MSC conditioned medium. Moreover, BM-MSCs-mediated tumor cell migration and invasion were hampered after treatment with AQP1 inhibitor. These data suggest that the recruitment of human BM-MSCs into the tumor microenvironment might cause OS and HCC cell migration and invasion through involvement of AQP1.

Highlights

  • Tumors are essentially composed of two interdependent compartments, namely tumor cells and surrounding stroma

  • The results showed that the aquaporin 1 (AQP1) level was increased in both tumor cell lines after treatment with bone marrow mesenchymal stem cells (BM-MSCs) conditioned medium

  • These data suggest that the recruitment of human BM-MSCs into the tumor microenvironment might cause OS and hepatocellular carcinoma (HCC) cell migration and invasion through involvement of AQP1

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Summary

Introduction

Tumors are essentially composed of two interdependent compartments, namely tumor cells and surrounding stroma. Recent studies reported that AQPs might play an important role in human. Role of bone-marrow derived mesenchymal stem cells (BM-MSCs) in tumor cell migration and Cancer stem cell (CSC); carcinoma associated fibroblasts (CAFs); dendritic cell (DC); myeloidinvasion. It has demonstrated that tumor cells secrete extracelullar vesicles containing different biomolecules (proteins, RNA, DNA and lipids) [6] that may be involved in promoting cancer progression and may represent targets for therapeutic intervention [7]. Such modifications in the microenvironment can stimulate tumor initiation, proliferation and metastasis. 2016, 17, 1102 of in osteosarcoma (OS) and hepatocellular carcinoma (HCC) progression due to BM-MSCs

Enhancement
Conditioned
Inhibition
Inhibition of AQP1 Hampers BM-MSCs-CM-Dependent OS and HCC Cell Invasion
Discussion
Cell Lines and Culture Conditions
Western Blot Analysis
Wound Healing Assay
Cell Invasion Assay
Statistics
Conclusions
Full Text
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