本研究では、胃癌細胞と脂肪由来幹細胞(ADSC)との細胞間相互作用に関する検討を実施した。ヒト大網よりADSCを分離、培養し、CAF（癌関連線維芽細胞）としての機能解析を行った結果、ADSCは癌細胞のEMTを誘導し、xenograftにおいて、間質内の線維化を誘導する事を確認した。胃癌細胞との共培養下において、sphere形成能を亢進させ、stemness関連蛋白の発現が増強し、癌幹細胞性獲得に関与している可能性が考えられた。更にマウス皮下腫瘍モデルにてADSCと胃癌細胞との共投与群では、5-FUの腫瘍縮小効果が抑制され、ADSCが化学療法抵抗性獲得に関与する事が示唆された。
Little is known regarding the influence of adipose tissue derived stem cells (ADSC) in gastric cancer (GC).We investigated the potential effects between GC cell lines and ADSC.
The sphere-forming efficiency of GC cells was significantly increased while directly co-cultured with ADSC. OCUM2MD3 cells generated subctaneous tumors increased in size after co-injection with ADSC in mouse model. Xenografts tissue revealed the expression of αSMA was increased in tumors generated by co-injection of OCUM2MD3 with ADSC in comparison with control tumors, which corresponds to the significant increase of fibrous area. The expressions of αSMA and FAP on ADSC were confirmed by fluorescent immunostaining. We also examined whether ADSC is associated with the chemo-sensitivity of OCUM2MD3 using 5-FU. ADSC enhance sphere formation and in vivo tumor growth of GC cells. ADSC also induced 5-FU-resistance, which suggests ADSC acts as CAF in tumor microenvironment of GC.
胃癌微小環境における脂肪由来幹細胞の機能解析と間質線維化制御への応用
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ME-PR-KINOSHITA-J-kaken 2018-4p.pdf
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