Cancer-Associated Fibroblast Proteins as Potential Targets against Colorectal Cancers.

Autor: Shah R; Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA.; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, WI 53705, USA., Johnson KA; Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA.; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, WI 53705, USA., Lippert AEL; Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA.; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, WI 53705, USA., Kraus SG; Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA.; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, WI 53705, USA., Emmerich PB; Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA., Pasch CA; Carbone Cancer Center, University of Wisconsin, Madison, WI 53705, USA., Zhang W; Carbone Cancer Center, University of Wisconsin, Madison, WI 53705, USA.; Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA., Matkowskyj KA; Carbone Cancer Center, University of Wisconsin, Madison, WI 53705, USA.; Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA., LeBeau AM; Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA.; Department of Radiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA., Deming DA; Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA.; McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin, Madison, WI 53705, USA.; Carbone Cancer Center, University of Wisconsin, Madison, WI 53705, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Sep 14; Vol. 16 (18). Date of Electronic Publication: 2024 Sep 14.
DOI: 10.3390/cancers16183158
Abstrakt: 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.
Databáze: MEDLINE
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