Vidergar Romana, Agostinis Chiara, Zacchi Paola, Mangogna Alessandro, Bossi Fleur, Zanconati Fabrizio, Confalonieri Marco, Ricci Giuseppe, Bulla Roberta
Department of Life Sciences, University of Trieste.
Institute for Maternal and Child Health, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Burlo Garofolo.
J Vis Exp. 2019 Jun 15(148). doi: 10.3791/58688.
It has been increasingly demonstrated that the tumor microenvironment plays an active role in neoplasia growth and metastasis. Through different pathways, tumor cells can efficiently recruit stromal, immune and endothelial cells by secreting stimulatory factors, chemokines and cytokines. In turn, these cells can alter the signaling properties of the microenvironment by releasing growth-promoting signals, metabolites and extracellular matrix components to sustain high proliferation and metastatic competence. In this context, we identify that the complement component C1q, highly expressed locally by a range of human malignant tumors, upon interacting with the extracellular matrix hyaluronic acid, strongly affects the behavior of primary cells isolated from human tumor specimens. Here, we describe a method to test how C1q bound to hyaluronic acid (HA) impacts tumor cell adhesion, underlying the fact that the biological properties of key components of the extracellular matrix (in this case HA) can be shaped by bioactive signals toward tumor progression.
越来越多的证据表明,肿瘤微环境在肿瘤生长和转移中发挥着积极作用。肿瘤细胞可通过分泌刺激因子、趋化因子和细胞因子,通过不同途径有效地募集基质细胞、免疫细胞和内皮细胞。反过来,这些细胞可通过释放促进生长的信号、代谢产物和细胞外基质成分来改变微环境的信号特性,以维持高增殖和转移能力。在此背景下,我们发现补体成分C1q在一系列人类恶性肿瘤中局部高表达,它与细胞外基质透明质酸相互作用后,会强烈影响从人类肿瘤标本中分离出的原代细胞的行为。在此,我们描述了一种测试结合透明质酸(HA)的C1q如何影响肿瘤细胞黏附的方法,这突出了一个事实,即细胞外基质的关键成分(在本例中为HA)的生物学特性可由促进肿瘤进展的生物活性信号塑造。