Abstract
Exosomes are a group of small membranous vesicles that are shed into the extracellular environment by tumoral or non-tumoral cells and contribute to cellular communication by delivering micro RNAs (miRNAs). In this study, we aimed to evaluate the role of exosomal miRNAs from colorectal cancer cell lines in tumorigenesis, by affecting cancer-associated fibroblasts (CAFs), which are vital constituents of the tumor microenvironment. To analyze the effect of exosomal miRNA on the tumor microenvironment, migration of the monocytic cell line THP-1 was evaluated via Transwell migration assay using CAFs isolated from colon cancer patients. The migration assay was performed with CAFs ± CCL7-blocking antibody and CAFs that were treated with exosomes isolated from colon cancer cell lines. To identify the associated exosomal miRNAs, miRNA sequencing and quantitative reverse transcription polymerase chain reaction were performed. The migration assay revealed that THP-1 migration was decreased in CCL7-blocking antibody-expressing and exosome-treated CAFs. Colon cancer cell lines contained miRNA let-7d in secreted exosomes targeting the chemokine CCL7. Exosomes from colorectal cancer cell lines affected CCL7 secretion from CAFs, possibly via the miRNA let-7d, and interfered with the migration of CCR2+ monocytic THP-1 cells in vitro.
Highlights
Colorectal cancer (CRC) is one of the most common cancers and accounts for 10% of cancerrelated deaths worldwide [1, 2]
HT-29 (American Type Culture Collection, ATCC, Manassas, VA, USA; HTB-38TM), SW480 (ATCC, CCL-228TM), Jurkat (ATCC, TIB-152TM), and THP-1 (Korea Cell Line Bank, Seoul, South Korea) cells were cultured at 37 ̊C in Roswell Park Memorial Institute medium 1640 (RPMI 1640, WELGENE, Gyeongsan-si, South Korea), including 10% fetal bovine serum (FBS, WELGENE), 100 U/mL penicillin G sodium, and 100 μg/mL streptomycin (Capricorn Scientific, Ebsdorfegrund, Germany)
The tumor microenvironment plays a significant role in tumor occurrence and development, and cell-to-cell communication is an essential mechanism in the tumor microenvironment, which maintains tissue homeostasis and normal cellular activities [39, 40]
Summary
Colorectal cancer (CRC) is one of the most common cancers and accounts for 10% of cancerrelated deaths worldwide [1, 2]. From 1990 to 2017, the age-standardized incidence rates of CRC increased globally [3]. On the basis of disability-adjusted life years, CRC has become the fourth leading cause of cancer burden, behind lung cancer, liver cancer, and stomach cancer [3]. Despite the improvements in diagnostic and surgical techniques and introduction of novel chemotherapeutic agents, the prognosis for CRC remains unsatisfactory, with a 13% 5-year survival rate in metastatic CRC due to the heterogeneity of response to therapy [4, 5].
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