title: Increase of α-SMA(+) and CK (+) cells as an early sign of epithelial-mesenchymal transition during colorectal carcinogenesis.
abstract: Our aim was to examine cell transition events by detecting the frequency of intrapithelial α-smooth muscle actin (SMA)(+)/cytokeratin (CK)(+) cells during colorectal adenoma-carcinoma sequence, in relation to E-cadherin expression. Our further aim was to determine the proliferative activity of intraepithelial α-SMA(+) cells. Histologically healthy, adenoma, and colorectal cancer (CRC) biopsy samples were taken during routine colonoscopy and were included into tissue microarrays (TMAs). Slides immunostained for Ki-67, α-SMA, E-cadherin and pan-cytokeratin were digitalized and analyzed by using a digital microscope software. The proportion of α-SMA(+)/CK(+) cells was significantly higher in CRC samples (3.34 ± 1.01%) compared to healthy (1.94 ± 0.69%) or adenoma (1.62 ± 0.78%) samples (p < 0.01). E-cadherin expression negatively correlated with the number of α-SMA(+) cells. The majority of intraepithelial α-SMA(+) cells were in the proliferative phase. During tumor progression, the appearance of dot-like α-SMA staining in CK positive cells may indicate the initial phase of the epithelial-to-mesenchymal transition (EMT). The high proportion of intraepithelial α-SMA(+) proliferating cells may refer to their increased plasticity compared to differentiated cells. The negative correlation between E-cadherin and intraepithelial α-SMA expression suggests that EMT is facilitated by a loss of epithelial cell contact.
authors.affiliation: Cell Analysis Laboratory, 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. valczg@yahoo.com
authors.forename: Gábor
authors.initials: G
authors.lastname: Valcz
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenács
authors.forename: Jeannette
authors.initials: J
authors.lastname: Molnár
authors.forename: Arpád V
authors.initials: AV
authors.lastname: Patai
authors.forename: Katalin
authors.initials: K
authors.lastname: Leiszter
authors.forename: Kinga
authors.initials: K
authors.lastname: Tóth
authors.forename: Barna
authors.initials: B
authors.lastname: Wichmann
authors.forename: Béla
authors.initials: B
authors.lastname: Molnár
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
mesh_terms: D000199:Actins / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism*; D008137:Longitudinal Studies; D009367:Neoplasm Staging; D011379:Prognosis; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D015820:Cadherins; D007633:Keratins