Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
Cancer Lett. 2017 Oct 1;405:90-99. doi: 10.1016/j.canlet.2017.07.024. Epub 2017 Jul 31.
The initiation and progression of malignant tumors are supported by their microenvironment: cancer cells per se cannot explain growth and formation of the primary or metastasis, and a combination of proliferating tumor cells, cancer stem cells, immune cells mesenchymal stromal cells and/or cancer-associated fibroblasts all contribute to the tumor bulk. The interaction between these multiple players, under different microenvironmental conditions of biochemical and physical stimuli (i.e. oxygen tension, pH, matrix mechanics), regulates the production and biological activity of several soluble factors, extracellular matrix components, and extracellular vesicles that are needed for growth, maintenance, chemoresistance and metastatization of cancer. In osteosarcoma, a very aggressive cancer of young adults characterized by the extensive need for more effective therapies, this aspect has been only recently explored. In this view, we will discuss the role of stroma, with a particular focus on the mesenchymal stroma, contributing to osteosarcoma progression through inherent features for homing, neovascularization, paracrine cross-feeding, microvesicle secretion, and immune modulation, and also by responding to the changes of the microenvironment that are induced by tumor cells. The most recent advances in the molecular cues triggered by cytokines, soluble factors, and metabolites that are partially beginning to unravel the axis between stromal elements of mesenchymal origin and osteosarcoma cells, will be reviewed providing insights likely to be used for novel therapeutic approaches against sarcomas.
肿瘤细胞本身并不能解释原发性或转移性肿瘤的生长和形成，增殖的肿瘤细胞、肿瘤干细胞、免疫细胞、间充质基质细胞和/或癌相关成纤维细胞的组合都有助于肿瘤的生长。在不同的生化和物理刺激（如氧张力、pH 值、基质力学）的微环境条件下，这些多种参与者之间的相互作用调节了几种可溶性因子、细胞外基质成分和细胞外囊泡的产生和生物学活性，这些都是肿瘤生长、维持、化疗耐药性和转移所必需的。在骨肉瘤中，这是一种非常侵袭性的青年人癌症，迫切需要更有效的治疗方法，这方面的研究直到最近才得到探索。在这种观点下，我们将讨论基质的作用，特别是间充质基质，通过归巢、血管生成、旁分泌交叉喂养、微泡分泌和免疫调节的固有特性，以及对肿瘤细胞诱导的微环境变化的反应，促进骨肉瘤的进展。本文将综述细胞因子、可溶性因子和代谢物触发的分子线索的最新进展，这些进展部分开始揭示间充质来源的基质成分与骨肉瘤细胞之间的轴，为针对肉瘤的新型治疗方法提供可能的见解。
