6. 肿瘤转移的分子调控 - 李红.pdfVIP

肿瘤转移的分子调控 李红李红 上上 海海 市市 肿肿 瘤瘤 研研 究究 所所 癌基因及相关基因国家重点实验室 TTumor mettasttasiis ?More than 90% of mortality from cancer is attributable to metastases, not the primary tumors from which these malignant lesions arise; ?Metastatic disease is largely incurable because of its systemic nature and the resistance of disseminated tumor cells to existingg therappeutic aggents;; ?It is hoped that a mechanistic understanding of metastasis will help develop better therapies and improve patient outcome. 基本概念基本概念 MetastasisMetastasis isis thethe processprocess wherebywhereby cancercancer cellscells spreadspread throughout the body, establishing new colonies in organs at a distance from the one where the primary tumor originated. TheThe majormajor routesroutesforfor tumortumor disseminationdissemination Lymphatic vessels: lymphatic Blood vessels: hematogenous Serosal surfaces: transcoelomic EpithelialEpithelial malignancies,malignancies, oror carcinomascarcinomas:: Typically begin their dissemination by the lymphatic route, with hematogenous metastasesmetastases occurringoccurring atat aa laterlater timetime. Bone and soft tissue tumors, or sarcomas: Preferentially metastasize by the hematogenous route. Mesotheliomas and ovarian carcinomas: Transcoelomic metastasis. PrincipalPrincipal stepssteps inin metastasismetastasis ? Detach from the primary mass; ? Invade the local host tissue stroma; ? Penetrate local lymphatic and blood vessels; ? Survive within the circulation; ? Become arrested in capillaries or venules of other organs; ? PenetratePenetrate thethe correspondingcorresponding parenchyma;parenchyma; ? Adapt to the newly colonized milieu or subvert the local microenvironment to suit its own needs; ? Divide to form the new tumor. OrganOrgan-specificspecific