In colorectal cancer (CRC), attempts to identify cancer cell-specific markers to guide antibody-mediated therapeutics have failed to uncover markers that are both exclusive to cancer tissues and abundant across CRCs. Alternatively, cancer-associated fibroblasts (CAFs), which are abundant in the tumor microenvironment and upregulate unique surface markers, are not found in healthy tissues. Here, we evaluated the expression patterns of CAF-associated proteins α-smooth muscle actin (αSMA), fibroblast activation protein (FAP), podoplanin (PDPN), matrix metalloproteinase-2 (MMP2), transgelin (TAGLN), and THY1. While αSMA and THY1 were abundant in cancer tissues, high abundance in normal tissues limited their targeting potential. FAP was present in 94.5% of primary and metastatic CRC tissues and absent in 93.7% of adjacent normal colon and liver tissues assessed. These results indicate that FAP is a promising target for antibody conjugates with potential for broad application in CRC. Co-expression analyses showed that CRCs simultaneously expressing high levels of PDPN, MMP2, and THY1 were enriched for immune-related signatures, indicating potential for antibody-mediated immune engagers. Overall, this work highlights the potential of CAF proteins to act as therapeutic targets for novel anticancer agents and become important therapeutic biomarkers.
在结直肠癌（CRC）研究中，寻找癌细胞特异性标记物以指导抗体介导治疗的尝试未能发现既在癌组织中特异性表达、又在各类CRC中广泛富集的标记物。相比之下，肿瘤相关成纤维细胞（CAF）在肿瘤微环境中大量存在，其表面标记物具有独特上调特性，且不存在于健康组织中。本研究评估了CAF相关蛋白α-平滑肌肌动蛋白（αSMA）、成纤维细胞活化蛋白（FAP）、平足蛋白（PDPN）、基质金属蛋白酶-2（MMP2）、转胶蛋白（TAGLN）及THY1的表达模式。虽然αSMA和THY1在癌组织中大量存在，但其在正常组织中的高丰度表达限制了其靶向潜力。在评估的组织样本中，FAP在94.5%的原发性及转移性CRC组织中表达，而在93.7%的癌旁正常结肠及肝组织中未见表达。这些结果表明FAP是抗体偶联药物的理想靶点，在CRC治疗中具有广泛应用潜力。共表达分析显示，同时高表达PDPN、MMP2和THY1的CRC样本富含免疫相关特征，提示其具有开发抗体介导免疫衔接器的潜力。总体而言，本研究揭示了CAF蛋白作为新型抗癌药物靶点的潜力，并有望成为重要的治疗性生物标志物。
Cancer-Associated Fibroblast Proteins as Potential Targets against Colorectal Cancers
肿瘤(癌症)患者之家