title: ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer.
abstract: Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT-PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Wellington Rd., Clayton, Victoria, Australia; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Thierry
authors.initials: T
authors.lastname: Jardé
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Wellington Rd., Clayton, Victoria, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kass
authors.affiliation: Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Staples
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Wellington Rd., Clayton, Victoria, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Lescesen
authors.affiliation: Department of Surgery, Cabrini Monash University, Malvern, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Carne
authors.affiliation: Department of Surgery, Cabrini Monash University, Malvern, Victoria, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Oliva
authors.affiliation: Department of Surgery, Cabrini Monash University, Malvern, Victoria, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McMurrick
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Wellington Rd., Clayton, Victoria, Australia.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Abud
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020893:Receptor, ErbB-3 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3