Interleukin-8 produced from cancer-associated fibroblasts suppresses proliferation of the OCUCh-LM1 cancer cell line

• Published in: BMC cancer Vol. 22; no. 1; p. 748
• Main Authors: Tanaka, Ryota, Kimura, Kenjiro, Eguchi, Shimpei, Ohira, Go, Tanaka, Shogo, Amano, Ryosuke, Tanaka, Hiroaki, Yashiro, Masakazu, Ohira, Masaichi, Kubo, Shoji
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08-07-2022; BioMed Central; BMC
• Subjects: Actin; Adenocarcinoma; Antibodies; Bile duct cancers; Bile ducts; Biliary tract; Cancer therapies; Cancer-associated fibroblast; Cancer-Associated Fibroblasts - metabolism; Carcinoma, Pancreatic Ductal - pathology; Cell growth; Cell Line; Cell Line, Tumor; Cell Proliferation; Chemokine receptors; Cholangiocarcinoma; Cholangitis; CXCR2 protein; Cytokines; Development and progression; Fibroblasts; Fibroblasts - metabolism; Gallbladder; Growth factors; Health aspects; Humans; Identification and classification; Interleukin 8; Interleukin-8 - metabolism; Medical prognosis; Metastasis; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; Patients; Physiological aspects; Proteins; R&D; Research & development; Retrospective Studies; Smooth muscle; Suppressive CAFs; Survival analysis; Tumor Microenvironment; Japan; Minneapolis Minnesota; United Kingdom > UK; United States > US; Cancer-associated fibroblast; Bile duct cancers; Interleukin-8; Suppressive CAFs; Pancreatic ductal adenocarcinoma
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09847-z

Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort.
We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines on cancer cell proliferation.
PDAC patients with positive αSMA expression showed significantly shorter overall survival and recurrence-free survival than αSMA-negative patients (p = 0.003, p = 0.009, respectively). BTC patients with positive αSMA expression showed better recurrence-free survival than αSMA-negative patients (p = 0.03). CAF-conditioned medium suppressed the proliferation of cancer cells for only OCUCh-LM1 cells and not PDAC cells. Blockage of Interleukin-8 (IL-8) or its receptor C-X-C motif chemokine receptor 2 (CXCR2) by antibodies canceled the suppressive effect of the IL-8.
CAFs are a good prognostic factor in BTC, but not for PDAC. Moreover, CAF-produced Interleukin-8 suppresses the proliferation of OCUCh-LM1 cell lines.