cis Interaction of the Cell Adhesion Molecule CEACAM1 with Integrin β3

Brümmer, Jens; Ebrahimnejad, Alireza; Flayeh, Raid; Schumacher, Udo; Löning, Thomas; Bamberger, Ana‐Maria; Wagener, Christoph

doi:10.1016/s0002-9440(10)61725-7

Cited by 69 publications

(66 citation statements)

References 54 publications

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“…It was shown that CEACAM1 expression varies in proliferating and quiescent epithelial cells and that this influences their proliferation (13). The colocalization and interaction of CEACAM1 with paxillin and integrin ␤ (3) recently were shown (14,15).…”

Section: Introductionmentioning

confidence: 96%

Dual Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Angiogenesis and Invasion of Human Urinary Bladder Cancer

Oliveira‐Ferrer

Tilki²,

Ziegeler³

et al. 2004

Cancer Research

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Here, we show that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in umbrella cells of bladder urothelium but is down-regulated in superficial bladder cancer, such as histologic tumor stage a (pTa) and transitional cell carcinoma in situ (pTis). Concurrently, CEACAM1 is up-regulated in the endothelia of adjacent angiogenic blood vessels. Mimicking the CEACAM1 down-regulation in the urothelium, CEACAM1 was silenced in bladder cancer cell lines 486p and RT4 using the small interfering RNA technique. CEACAM1 downregulation was confirmed at the protein level by Western blot analyses. CEACAM1 silencing leads to a significant up-regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D in quantitative reverse transcription-PCR. Correspondingly, supernatants from the CEACAM1-overexpressing bladder cancer cell lines reduce, but those from CEACAM1 silencing induce endothelial tube formation and potentiate the morphogenetic effects of VEGF. These data suggest that the epithelial down-regulation of CEACAM1 induces angiogenesis via increased expression of VEGF-C and VEGF-D. Inversely, CEACAM1 is up-regulated in endothelial cells of angiogenic blood vessels. This in turn is involved in the switch from noninvasive and nonvascularized to invasive and vascularized bladder cancer. CEACAM1 appears to be a promising endothelial target for bladder cancer therapy.

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Section: Introductionmentioning

confidence: 96%

Dual Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Angiogenesis and Invasion of Human Urinary Bladder Cancer

Oliveira‐Ferrer

Tilki²,

Ziegeler³

et al. 2004

Cancer Research

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show abstract

“…Additionally, CEACAM1 expression varies in proliferating and quiescent epithelial cells and this influences their proliferation (Singer et al, 2000). CEACAM1 is colocalized and interacts with paxillin and integrin beta(3) (Ebrahimnejad et al, 2000;Brummer et al, 2001), which are important for the formation of adhesion complexes and cell-matrix interactions.…”

Section: Introductionmentioning

confidence: 99%

CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate cancer

et al. 2006

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We demonstrate here that epithelial carcinoembryonic antigen (CEA)-related cell adhesion molecule-1 (CEA-CAM1) downregulation in prostate intraepithelial neoplasia (PIN) is inversely correlated with its upregulation in adjacent blood vessels. CEACAM1 silencing in prostate cancer cell line DU-145 via small interfering ribonucleic acid (siRNA) increased but its overexpression suppressed the expression of angiogenic/lymphangiogenic factors such as vascular endothelial growth factor (VEGF)-A, -C and -D, and angiogenic inhibitor collagen 18/ endostatin. Furthermore, CEACAM1 overexpression in DU-145 cells increased but CEACAM1 silencing reduced angiopoietin-1 expression. Inverse relation was found for angiopoietin-2. Supernatant of CEACAM1-overexpressing DU-145 suppressed but that of CEACAM1-silenced increased the VEGF-induced endothelial tubes. Electron microscopically the majority of PIN-associated blood vessels was structurally destabilized exhibiting endothelial fenestration, trans-and inter-endothelial gaps. In some PIN areas, invasion of single tumor cells into the destabilized blood vessels was observed. These data show that disappearance of epithelial CEACAM1 in PIN is accompanied by its upregulation in adjacent vasculature which apparently correlates with vascular destabilization and increased vascularization of prostate cancer. Strategies to either conserve the epithelial CEACAM1 or to target endothelial CEACAM1 might be useful for an anti-angiogenic therapy of prostate cancer.

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“…An apparently gradual increase in CD66 expression in cutaneous melanocytic lesions in more advanced stages of neoplastic progression was observed, indicating that CD66 may play an important role in the development and progression of melanoma. Furthermore, this molecule interacts with integrins (especially with beta-3 subunit) and this interaction appears to be important in cell migration and metastasis [43]. The CD146 molecule was first identified as a cell adhesion molecule specific for melanoma and capable of providing homologous and heterologous interactions between neoplastic melanocytes and endothelial cells in a calcium-independent manner [14].…”

Section: Integrins Referencementioning

confidence: 99%