Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion

Shin Kibe, Kenoki Ouchida, Yohei Ando, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Takashi Okumura, Chika Iwamoto, Koji Shindo, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Masaya Shimamoto, Ohtsuka Takao, Kazuhiro Mizumoto, Yoshinao Oda, Masafumi Nakamura

Research output: Contribution to journalArticle

Abstract

The pancreas is an organ prone to inflammation, fibrosis, and atrophy because of an abundance of acinar cells that produce digestive enzymes. A characteristic of pancreatic cancer is the presence of desmoplasia, inflammatory cell infiltration, and cancer-associated acinar atrophy (CAA) within the invasive front. CAA is characterized by a high frequency of small ducts and resembles acinar-to-ductal metaplasia (ADM). However, the clinical significance of changes in acinar morphology, such as ADM with acinar atrophy, within the tumor microenvironment remains unclear. Here, we find that ADM within the invasive front of tumors is associated with cell invasion and desmoplasia in an orthotopic mouse model of pancreatic cancer. An analysis of resected human tumors revealed that regions of cancer-associated ADM were positive for TGFα and that this TGFα expression was associated with primary tumor size and shorter survival times. Gene expression analysis identified distinct phenotypic profiles for cancer-associated ADM, sporadic ADM and chronic pancreatitis ADM. These findings suggest that the mechanisms driving ADM differ according to the specific tissue microenvironment and that cancer-associated ADM and acinar atrophy contribute to tumor cell invasion of the local pancreatic parenchyma.

Original languageEnglish
Pages (from-to)70-81
Number of pages12
JournalCancer Letters
Volume444
DOIs
Publication statusPublished - Mar 1 2019

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Metaplasia
Pancreatic Neoplasms
Atrophy
Neoplasms
Tumor Microenvironment
Acinar Cells
Chronic Pancreatitis
Pancreas
Fibrosis
Inflammation
Gene Expression
Survival
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion. / Kibe, Shin; Ouchida, Kenoki; Ando, Yohei; Takesue, Shin; Nakayama, Hiromichi; Abe, Toshiya; Endo, Sho; Koikawa, Kazuhiro; Okumura, Takashi; Iwamoto, Chika; Shindo, Koji; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Shimamoto, Masaya; Takao, Ohtsuka; Mizumoto, Kazuhiro; Oda, Yoshinao; Nakamura, Masafumi.

In: Cancer Letters, Vol. 444, 01.03.2019, p. 70-81.

Research output: Contribution to journalArticle

Kibe, Shin ; Ouchida, Kenoki ; Ando, Yohei ; Takesue, Shin ; Nakayama, Hiromichi ; Abe, Toshiya ; Endo, Sho ; Koikawa, Kazuhiro ; Okumura, Takashi ; Iwamoto, Chika ; Shindo, Koji ; Moriyama, Taiki ; Nakata, Kohei ; Miyasaka, Yoshihiro ; Shimamoto, Masaya ; Takao, Ohtsuka ; Mizumoto, Kazuhiro ; Oda, Yoshinao ; Nakamura, Masafumi. / Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion. In: Cancer Letters. 2019 ; Vol. 444. pp. 70-81.
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AU - Shimamoto, Masaya

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