González-González Laura, Alonso Javier
Unidad de Tumores Sólidos Infantiles, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain.
Front Oncol. 2018 Jun 12;8:225. doi: 10.3389/fonc.2018.00225. eCollection 2018.
Tumor microenvironment is considered nowadays as one of the main players in cancer development and progression. Tumor microenvironment is highly complex and consists of non-tumor cells (i.e., cancer-associated fibroblast, endothelial cells, or infiltrating leukocytes) and a large list of extracellular matrix proteins and soluble factors. The way that microenvironment components interact among them and with the tumor cells is very complex and only partially understood. However, it is now clear that these interactions govern and modulate many of the cancer hallmarks such as cell proliferation, the resistance to death, the differentiation state of tumor cells, their ability to migrate and metastasize, and the immune response against tumor cells. One of the microenvironment components that have emerged in the last years with strength is a heterogeneous group of multifaceted proteins grouped under the name of matricellular proteins. Matricellular proteins are a family of non-structural matrix proteins that regulate a variety of biological processes in normal and pathological situations. Many components of this family such as periostin (POSTN), osteopontin (SPP1), or the CNN family of proteins have been shown to regulate key aspect of tumor biology, including proliferation, invasion, matrix remodeling, and dissemination to pre-metastatic niches in distant organs. Matricellular proteins can be produced by tumor cells themselves or by tumor-associated cells, and their synthesis can be affected by intrinsic and/or extrinsic tumor cell factors. In this review, we will focus on the role of POSTN in the development and progression of cancer. We will describe their functions in normal tissues and the mechanisms involved in their regulation. We will analyze the tumors in which their expression is altered and their usefulness as a biomarker of tumor progression. Finally, we will speculate about future directions for research and therapeutic approaches targeting POSTN.
如今，肿瘤微环境被认为是癌症发生和发展的主要因素之一。肿瘤微环境高度复杂，由非肿瘤细胞（即癌症相关成纤维细胞、内皮细胞或浸润性白细胞）以及大量细胞外基质蛋白和可溶性因子组成。微环境成分之间以及与肿瘤细胞之间相互作用的方式非常复杂，目前仅部分为人所知。然而，现在很清楚的是，这些相互作用控制和调节许多癌症特征，如细胞增殖、对死亡的抗性、肿瘤细胞的分化状态、它们迁移和转移的能力以及针对肿瘤细胞的免疫反应。近年来强势出现的微环境成分之一是一组多面蛋白的异质群体，统称为基质细胞蛋白。基质细胞蛋白是一类非结构性基质蛋白家族，在正常和病理情况下调节多种生物学过程。该家族的许多成分，如骨膜蛋白（POSTN）、骨桥蛋白（SPP1）或CNN蛋白家族，已被证明可调节肿瘤生物学的关键方面，包括增殖、侵袭、基质重塑以及向远处器官的前转移微环境扩散。基质细胞蛋白可由肿瘤细胞自身或肿瘤相关细胞产生，其合成可受内在和/或外在肿瘤细胞因子影响。在本综述中，我们将重点关注POSTN在癌症发生和发展中的作用。我们将描述其在正常组织中的功能以及其调节所涉及的机制。我们将分析其表达发生改变的肿瘤以及其作为肿瘤进展生物标志物的效用。最后，我们将推测针对POSTN的未来研究方向和治疗方法。
