title: INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors.
abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5-RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.
authors: Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. hmashima1-tky@umin.ac.jp
authors: Hirosato
authors: H
authors: Mashima
authors: Hideki
authors: H
authors: Ohno
authors: Yumi
authors: Y
authors: Yamada
authors: Toshitaka
authors: T
authors: Sakai
authors: Hirohide
authors: H
authors: Ohnishi
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018358:Neuroendocrine Tumors / Q000378:metabolism; D019899:Paracrine Communication; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D012007:Rectum / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; C480239:RXFP4 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide