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Trefoil factor 1 suppresses stemness and enhances chemosensitivity of pancreatic cancer.
Yamaguchi, Junpei; Kokuryo, Toshio; Yokoyama, Yukihiro; Oishi, Shunsuke; Sunagawa, Masaki; Mizuno, Takashi; Onoe, Shunsuke; Watanabe, Nobuyuki; Ogura, Atsushi; Ebata, Tomoki.
Afiliación
  • Yamaguchi J; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Kokuryo T; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Yokoyama Y; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Oishi S; Institute of Transformative Bio-Molecules, Nagoya University, Nagoya, Japan.
  • Sunagawa M; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Mizuno T; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Onoe S; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Watanabe N; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Ogura A; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Ebata T; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Med ; 13(11): e7395, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38872370
ABSTRACT
BACKGROUND AND

AIMS:

Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial-mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor-suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer.

METHODS:

To investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1-Cre/LSL-KRASG12D/LSL-p53R172H/TFF1-/-) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model.

RESULTS:

The deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine-induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells in vitro. In vivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness.

CONCLUSION:

These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Resistencia a Antineoplásicos / Transición Epitelial-Mesenquimal / Factor Trefoil-1 Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Resistencia a Antineoplásicos / Transición Epitelial-Mesenquimal / Factor Trefoil-1 Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos