PDF(Pubmed)
Abstract：
Resistance is a major problem with effective cancer treatment and the stroma forms a significant portion of the tumor mass but traditional drug screens involve cancer cells alone. Cancer-associated fibroblasts (CAFs) are a major tumor stroma component and its secreted proteins may influence the function of cancer cells. The majority of secretome studies compare different cancer or CAF cell lines exclusively. Here, we present the direct characterization of the secreted protein profiles between CAFs and KRAS mutant-cancer cell lines from colorectal, lung, and pancreatic tissues using multiplexed mass spectrometry. 2573 secreted proteins were annotated, and differential analysis highlighted understudied CAF-enriched secreted proteins, including Wnt family member 5B (WNT5B), in addition to established CAF markers, such as collagens. The functional role of CAF secreted proteins was explored by assessing its effect on the response to 97 anticancer drugs since stromal cells may cause a differing cancer drug response, which may be missed on routine drug screening using cancer cells alone. CAF secreted proteins caused specific effects on each of the cancer cell lines, which highlights the complexity and challenges in cancer treatment and so the importance to consider stromal elements.
摘要：
耐药性是有效癌症治疗的主要问题，基质构成了肿瘤块的重要部分，但传统的药物筛选仅涉及癌细胞。癌相关成纤维细胞（CAFs）是肿瘤基质的主要成分，其分泌蛋白可能影响癌细胞的功能。大多数分泌组研究仅比较不同的癌症或CAF细胞系。这里,我们提供了来自结直肠的CAFs和KRAS突变癌细胞系之间的分泌蛋白谱的直接表征，肺，和使用多重质谱的胰腺组织。2573个分泌蛋白被注释，差异分析强调了未研究的富含CAF的分泌蛋白，包括Wnt家族成员5B（WNT5B），除了已建立的CAF标记，如胶原蛋白。通过评估CAF分泌蛋白对97种抗癌药物反应的影响来探索CAF分泌蛋白的功能作用，因为基质细胞可能会引起不同的癌症药物反应。在单独使用癌细胞的常规药物筛查中可能会遗漏。CAF分泌蛋白对每个癌细胞系产生特定的影响，这突出了癌症治疗的复杂性和挑战，以及考虑基质元素的重要性。
