去勢抵抗性前立腺癌への進展機構としてホルモン療法後に生じる癌間質構造の多様性に着目した。癌間質を構成するactiveな線維芽細胞は細胞増殖因子やサイトカイン、細胞外マトリックスの構築などを介し、前立腺癌の悪性・進展を促進させる。ひと前立腺癌患者由来線維芽細胞とヒト前立腺癌細胞をin vitro共培養したところ、いくつかの線維芽細胞は癌細胞における癌抑制遺伝子の発現量を有意に低下させた。一方で、癌遺伝子の発現量を有意に増加させる線維芽細胞も確認された。つまり、activeな線維芽細胞は癌細胞の増殖に関わるだけでなく、癌細胞の分化状態をも変化させ、去勢抵抗性の獲得に寄与している可能性が示唆された。
In the tumor microenviroment, heterogeneous stromal component of prostate cancer (PCa) tissue contains multiple populations of fibroblasts that are associated with tumorigenesis. Fibroblasts secret a number of growth factors, cytokines, ECM proteins, and miRNAs that stimulate progression of PCa cells. In this study, we investigated the effects of fibroblasts on androgen-sensitive human PCa cell line LNCaP focusing on the expression of cancer-related genes. As for tumor suppressor genes, mRNA expression of NKX3-1 in LNCaP cells was decreased by co-culturing with fibroblasts. As for oncogenes, mRNA expressions of NFKB1 and SRC in LNCap cells was increased by co-culturing with fibroblasts. Our data showed that mRNA expressions of cancer-related genes in LNCaP cells were highly disturbed by co-culturing with fibroblasts. The use of PCa patients-derived fibroblasts may allow us to investigate the characteristics of aggressive fibroblasts in the development of castration-resistant PCa.
前立腺癌細胞分化の揺らぎによる去勢抵抗性獲得機構
2020RP0028
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