title: CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells.
abstract: Although previous in vitro studies predicted that CCN5/WISP-2 may act as an anti-invasive gene in breast cancer, the distribution pattern of CCN5 in breast cancer samples is conflicting. Thus, we systematically investigated the CCN5 expression profile in noninvasive and invasive breast tumor samples and its functional relevance in breast cancer progression. The studies showed that CCN5 expression is biphasic, such that in normal samples CCN5 expression is undetectable, whereas its expression is markedly increased in noninvasive breast lesions, including atypical ductal hyperplasia and ductal carcinoma in situ. Further, CCN5 mRNA and protein levels are significantly reduced as the cancer progresses from a noninvasive to invasive type. Additionally, we showed that CCN5 mRNA and protein level was almost undetectable in poorly differentiated cancers compared with the moderately or well-differentiated samples and its expression inversely correlated with lymph node positivity. The result was further supported by evaluating the RNA expression profile in microdissected sections using real-time PCR analysis. Therefore, our data suggest a protective function of CCN5 in noninvasive breast tumor cells. This hypothesis was further supported by our in vitro studies illuminating that CCN5 is a negative regulator of migration and invasion of breast cancer cells, and these events could be regulated by CCN5 through the modulation of the expression of genes essential for an invasive front. These include Snail-E-cadherin signaling and matrix metalloproteinase (MMP)-9 and MMP-2. Collectively, these studies suggest that the protective effect of CCN5 in breast cancer progression may have important therapeutic implications.
authors.affiliation: Cancer Research Unit, Veterans Affairs Medical Center, Kansas City, Missouri 64128, USA.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Banerjee
authors.forename: Gopal
authors.initials: G
authors.lastname: Dhar
authors.forename: Inamul
authors.initials: I
authors.lastname: Haque
authors.forename: Suman
authors.initials: S
authors.lastname: Kambhampati
authors.forename: Smita
authors.initials: S
authors.lastname: Mehta
authors.forename: Krishanu
authors.initials: K
authors.lastname: Sengupta
authors.forename: Ossama
authors.initials: O
authors.lastname: Tawfik
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Phillips
authors.forename: Sushanta K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D055511:CCN Intercellular Signaling Proteins; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D055511:CCN Intercellular Signaling Proteins; C413323:CCN5 protein, human; D015820:Cadherins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9