Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment

• Published in: Cancer science 2023-11, Vol.114 (11), p.4286-4298
• Main Authors: Kashiwagi, Ryosuke, Funayama, Ryo, Aoki, Shuichi, Matsui, Aya, Klein, Sebastian, Sato, Yukihiro, Suzuki, Tsubasa, Murakami, Keigo, Inoue, Koetsu, Iseki, Masahiro, Masuda, Kunihiro, Mizuma, Masamichi, Naito, Hisamichi, Duda, Dan G, Unno, Michiaki, Nakayama, Keiko
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Cell growth; Cell proliferation; Collagen; Collagen Type XVII; Fibroblasts; Gene expression; Humans; Immune response; Laboratory animals; Mice; Mice, Inbred C57BL; Original; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; RNA; Sequence analysis; Skin diseases; Statistical analysis; Stromal cells; Survival analysis; Tumor cell lines; Tumor cells; Tumor microenvironment; Tumor Microenvironment - genetics; Tumorigenesis; Tumors; Wnt protein
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15952

Expression of the gene for collagen XVII (COL17A1) in tumor tissue is positively or negatively associated with patient survival depending on cancer type. High COL17A1 expression is thus a favorable prognostic marker for breast cancer but unfavorable for pancreatic cancer. This study explored the effects of COL17A1 expression on pancreatic tumor growth and their underlying mechanisms. Analysis of published single-cell RNA-sequencing data for human pancreatic cancer tissue revealed that COL17A1 was expressed predominantly in cancer cells rather than surrounding stromal cells. Forced expression of COL17A1 did not substantially affect the proliferation rate of the mouse pancreatic cancer cell lines KPC and AK4.4 in vitro. However, in mouse homograft tumor models in which KPC or AK4.4 cells were injected into syngeneic C57BL/6 or FVB mice, respectively, COL17A1 expression promoted or suppressed tumor growth, respectively, suggesting that the effect of COL17A1 on tumor growth was influenced by the tumor microenvironment. RNA-sequencing analysis of tumor tissue revealed effects of COL17A1 on gene expression profiles (including the expression of genes related to cell proliferation, the immune response, Wnt signaling, and Hippo signaling) that differed between C57BL/6-KPC and FVB-AK4.4 tumors. Our data thus suggest that COL17A1 promotes or suppresses cancer progression in a manner dependent on the interaction of tumor cells with the tumor microenvironment.