Foidart J M, Polette M, Birembaut P, Noel A
Service de Biologie Générale et Cellulaire, Université de Liège, Belgique.
Bull Acad Natl Med. 1994 Mar;178(3):533-42; discussion 542-4.
Tumor progression is influenced by extracellular matrices and by soluble factors or cytokines locally produced by host tissue cells (fibroblasts, immune cells ...). Such factors may also accumulate in close association with some extracellular matrix molecules in the tumor. They may also be unmasked during breaking down of extracellular matrices. The most insidious aspect of tumors is their propensity to locally invade normal tissues of the host and to form secondary foci in organs at distant sites from the primary tumor called metastases. During this process, invasive cells come into contact with host tissue cells such as fibroblasts, endothelial cells, macrophages, lymphocytes. These cells are not the passive witnesses of the metastatic cascade but actively participate to the malignant invasion. Through soluble messages (cytokines) and through insoluble molecules of the extracellular matrix, neoplastic and normal cells mutually modulate their activities. Cancer cells regulate the biosynthetic activities of fibroblasts and alter in this way the scaffold of the tumor. Reciprocally, host cells secrete extracellular matrix proteins and cytokines which influence the growth and activities of tumor cells. They also produce at the periphery of tumor cells proteolytic enzymes which promote host tissue destruction and cancerous cells migration. Among these enzymes, matrix metalloproteinases appear to play a key role during invasion and metastasis. Tumors represent thus a complex ecosystem. Tumor cells interact with several components of the extracellular matrix and with host cells (immune cells, fibroblasts, endothelial cells). Such multiple cell-cell and cell-matrix interactions condition angiogenesis, tumor growth, destruction of host tissues, local migration of cancer cells and their metastatic dissemination. It is probable that a precise knowledge of the genes which are selectively activated in tumors under the influence of the host cells or of the tumor cells will allow to define new therapeutic strategies. These treatments will aim not at destroying the metastatic neoplastic cells but at preventing their growth by interfering with their microenvironment.
肿瘤进展受细胞外基质以及宿主组织细胞（成纤维细胞、免疫细胞等）局部产生的可溶性因子或细胞因子影响。这些因子也可能与肿瘤中的一些细胞外基质分子紧密结合而积聚。它们也可能在细胞外基质分解过程中被暴露出来。肿瘤最隐匿的方面在于其倾向于局部侵袭宿主的正常组织，并在远离原发肿瘤的器官中形成称为转移灶的继发性病灶。在此过程中，侵袭性细胞会与宿主组织细胞如成纤维细胞、内皮细胞、巨噬细胞、淋巴细胞接触。这些细胞并非转移级联反应的被动旁观者，而是积极参与恶性侵袭。通过可溶性信号（细胞因子）以及细胞外基质的不溶性分子，肿瘤细胞与正常细胞相互调节彼此的活性。癌细胞调节成纤维细胞的生物合成活性，从而改变肿瘤的支架结构。相反，宿主细胞分泌影响肿瘤细胞生长和活性的细胞外基质蛋白和细胞因子。它们还在肿瘤细胞周边产生蛋白水解酶，促进宿主组织破坏和癌细胞迁移。在这些酶中，基质金属蛋白酶在侵袭和转移过程中似乎起着关键作用。因此，肿瘤代表了一个复杂的生态系统。肿瘤细胞与细胞外基质的多个成分以及宿主细胞（免疫细胞、成纤维细胞、内皮细胞）相互作用。这种多种细胞 - 细胞和细胞 - 基质相互作用决定了血管生成、肿瘤生长、宿主组织破坏、癌细胞局部迁移及其转移扩散。有可能精确了解在宿主细胞或肿瘤细胞影响下在肿瘤中选择性激活的基因，将有助于确定新的治疗策略。这些治疗的目标不是破坏转移性肿瘤细胞，而是通过干扰其微环境来阻止其生长。
