Authors: Yoshitaka Suda Shinya Neri Hiroko Hashimoto Youichi Higuchi Masayuki Ishibashi Masato Sugano Kenkichi Masutomi Masahiro Tsuboi Atsushi Ochiai Genichiro Ishii
Publish Date: 2016/04/27
Volume: 142, Issue: 7, Pages: 1487-1498
Abstract
Cancerassociated fibroblasts CAFs consist of heterogeneous cell population in terms of their differentiation potential The functional differences in tumor progression between CAFs with mesenchymal stem/progenitor cells MSCs/MPCs characteristics and CAFs without MSCs/MPCs characteristics are not clarifiedCAFs and vascular adventitial fibroblasts VAFs which contain MSCs/MPCs were isolated from nine primary lung cancers and were cultured in osteogenic or adipogenic medium to assess their multilineage differentiation Next we established nine singlecellderived clones from the primary culture of CAFs and examined their differentiation potential The effects of each singlecellderived clone on the proliferation and migration of lung adenocarcinoma cell line A549 were analyzedThe nine samples of VAFs and CAFs showed various degrees of osteogenic differentiation Although the VAFs displayed the ability to undergo adipogenic differentiation all cases of the CAFs did not CAFs clones presented varying degrees of osteogenic differentiation Four clones displayed comparable levels of osteogenic potential with that of the VAFs and two clones were completely negative As compared to the CAFs clones that possessed lower osteogenic potential CAFs clones with higher osteogenic potential did not confer proliferative activity in A549 cells On the contrary these clones significantly promoted the migration of A549 cells as compared to the clones with lower osteogenic potentialOur studies clearly indicate that CAFs derived from lung cancer are heterogeneous population that consists of cells with varying osteogenic potentials and that CAFs with higher osteogenic potential have a greater tumorpromoting function through the enhancement of cancer cell migrationThis work was supported by National Cancer Center Research and Development Fund 23A12 and 26A16 the Foundation for the Promotion of Cancer Research 3rdTerm Comprehensive 10Year Strategy for Cancer Control Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation and JSPS KAKENHI 24659185
Keywords: