骨微小環境での前立腺癌の増殖におけるMMP7・MMP13の役割と治療標的としての有用性(特別講演V, 第152回名古屋市立大学医学会例会)

概要

論文の詳細を見る
Bone metastases are the most critical complications with advanced prostate cancer and conventional therapies do not allow a curative outcome for prostate cancer bone metastasis. Elucidation of molecular mechanisms that regulate prostate tumor growth in the bone microenvironment is essential for development of new therapeutic approaches to prevent bone metastasis. Recently, we developed a syngenic rat model that mimics human prostate cancer bone metastasis with respect to tumor stromal interaction. Microarray analysis of tissue from the tumor-bone interface identified the aberrant regulation of several genes including MMP7 and MMP13. We have demonstrated that MMP-7 was expressed by osteoclasts and cleaved RANKL to soluble active from that important in promoting osteoclast activation and bone resorption. MMP13 was expressed by osteoclasts and activate TGF β derived from bone matrix, which promoted osteoclast activation and bone resorption and tumor cell proliferation in the bone microenvironments. Here we have clearly defined how MMP7 and MMP13 can contribute to the tumor cell proliferaction and formation of osteolytic and osteoblastic lesions in the bone microenvironment thus making MMP7 and MMP13 an inviting theraputic target.
名古屋市立大学の論文
2009-01-30