Facilitating cholangiocarcinoma inhibition by targeting CD47

Kulthida Vaeteewoottacharn; Sakda Waraasawapati; Phattarin Pothipan; Ryusho Kariya; Saowaluk Saisomboon; Supawadee Bunthot; Chawalit Pairojkul; Kanlayanee Sawanyawisuth; Kazuhiko Kuwahara; Sopit Wongkham; Seiji Okada

Experimental and Molecular Pathology (Dec 2024)

Facilitating cholangiocarcinoma inhibition by targeting CD47

Kulthida Vaeteewoottacharn,
Sakda Waraasawapati,
Phattarin Pothipan,
Ryusho Kariya,
Saowaluk Saisomboon,
Supawadee Bunthot,
Chawalit Pairojkul,
Kanlayanee Sawanyawisuth,
Kazuhiko Kuwahara,
Sopit Wongkham,
Seiji Okada

Affiliations

Kulthida Vaeteewoottacharn: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand; Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan; Correspondence to: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mittapap Road, Khon Kaen 40002, Thailand.
Sakda Waraasawapati: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Phattarin Pothipan: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Ryusho Kariya: Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan
Saowaluk Saisomboon: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand; Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
Supawadee Bunthot: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Chawalit Pairojkul: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Kanlayanee Sawanyawisuth: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
Kazuhiko Kuwahara: Department of Diagnostic Pathology, Kindai University Hospital, Osaka 589-8511, Japan
Sopit Wongkham: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
Seiji Okada: Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan; Correspondence to: Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan.

Journal volume & issue: Vol. 140
p. 104935

Abstract

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Immune evasion is one of the mechanisms by which cancer cells acquire immunity during cancer development and progression. One of these is the increased expression of cluster of differentiation 47 (CD47), a transmembrane glycoprotein that protects cells from phagocytic elimination. The interaction between CD47 and signal regulatory protein alpha (SIRPα) on macrophages alleviates the phagocytic signal. The present group previously reported high CD47 expression in cholangiocarcinoma (CCA), a major health problem in Thailand and East Asia, and that blocking CD47 using anti-CD47 antibodies promoted the removal of CCA. However, the mechanism through which CD47 inhibition attenuates CCA growth remains unclear. This study explored the clinical significance of targeting CD47 in CCA. Expression levels of CD47 and the macrophage marker CD68 were determined in CCA tissues by immunohistochemistry and correlated with clinical parameters. The role of CD47 in CCA cells was established using CD47-deficient KKU-213A CCA clones in vitro and in vivo. The results showed that CD47 was highly expressed in CCA tissues and significantly correlated with lymph node metastasis (P = 0.038). Moderate-to-dense CD68-positive infiltrating cells in CCA tissues were significantly associated with shorter survival of patients (P = 0.019) and were an independent prognostic factor of CCA patients as determined by the Cox proportional hazard model (hazard ratio, 2.040; 95 % confidence interval, 1.109–3.752; P = 0.022). Three CD47-deficient KKU-213A clones (#19, #23, and #28) were generated. The elimination of CD47 did not affect cell proliferation but increased monocyte-derived macrophage-mediated phagocytosis in vitro. Decreased tumor weights and volumes were observed in mice injected with CD47-deficient CCA clones. This revealed a significant role for CD47 in CCA, with a focus on protecting cancer cells from macrophage phagocytosis.

Published in Experimental and Molecular Pathology

ISSN: 1096-0945 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Pathology
Website: https://www.sciencedirect.com/journal/experimental-and-molecular-pathology

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