Down-regulation of CEACAM1 in human prostate cancer: Correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition

Busch, Christer; Hanssen, Tove Aminda; Wagener, Christoph; Öbrink, Björn

doi:10.1053/hupa.2002.32218

Cited by 98 publications

(89 citation statements)

References 20 publications

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“…Many different functions were attributed to the CEACAM1 protein. It was shown that the CEACAM1 protein exhibits antiproliferative properties in carcinomas of colon (24) and prostate (25). Additional data support the central involvement of CEACAM1 in angiogenesis (26), metastasis (27), and insulin clearance (28).…”

Section: Inhibition Of Human Tumor-infiltrating Lymphocyte Effector Fmentioning

confidence: 54%

Inhibition of Human Tumor-Infiltrating Lymphocyte Effector Functions by the Homophilic Carcinoembryonic Cell Adhesion Molecule 1 Interactions

Markel

Seidman

Stern

et al. 2006

The Journal of Immunology

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Efficient antitumor immune response requires the coordinated function of integrated immune components, but is finally exerted by the differentiated effector tumor-infiltrating lymphocytes (TIL). TIL cells comprise, therefore, an exciting platform for adoptive cell transfer (ACT) in cancer. In this study, we show that the inhibitory carcinoembryonic Ag cell adhesion molecule 1 (CEACAM1) protein is found on virtually all human TIL cells following preparation protocols of ACT treatment for melanoma. We further demonstrate that the CEACAM1 homophilic interactions inhibit the TIL effector functions, such as specific killing and IFN-γ release. These results suggest that CEACAM1 may impair in vivo the antitumor response of the differentiated TIL. Importantly, CEACAM1 is commonly expressed by melanoma and its presence is associated with poor prognosis. Remarkably, the prolonged coincubation of reactive TIL cells with their melanoma targets results in increased functional CEACAM1 expression by the surviving tumor cells. This mechanism might be used by melanoma cells in vivo to evade ongoing destruction by tumor-reactive lymphocytes. Finally, CEACAM1-mediated inhibition may hinder in many cases the efficacy of TIL ACT treatment of melanoma. We show that the intensity of CEACAM1 expression on TIL cells constantly increases during ex vivo expansion. The implications of CEACAM1-mediated inhibition of TIL cells on the optimization of current ACT protocols and on the development of future immunotherapeutic modalities are discussed.

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Section: Inhibition Of Human Tumor-infiltrating Lymphocyte Effector Fmentioning

confidence: 54%

Inhibition of Human Tumor-Infiltrating Lymphocyte Effector Functions by the Homophilic Carcinoembryonic Cell Adhesion Molecule 1 Interactions

Markel

Seidman

Stern

et al. 2006

The Journal of Immunology

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“…The present results show that the CEA-related cell adhesion molecule CEACAM1, which is present at the luminal surface of normal prostate epithelium, is Busch et al (2002), but the current work focuses on the early stage of prostate cancer, the PIN. High-grade PIN is considered to be a noninvasive precancerous form of prostate cancer (Mazzucchelli et al, 2000) and is associated with an increase in vascular density suggesting an activation of angiogenesis in this precancerous stage of prostate tumor (Mazzucchelli et al, 2000;Huss et al, 2001).…”

Section: Discussionmentioning

confidence: 73%

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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“…Indeed introduction into tumor cells derived from these carcinomas has been shown to slow tumor progression. For example, human prostate and colon cancer cells show diminished tumorigenesis when transfected with CEACAM1 (Hsieh et al, 1995;Kunath et al, 1995;Luo et al, 1999;Busch et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases

Winer

et al. 2006

Oncogene

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Down-regulation of CEACAM1 in human prostate cancer: Correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition

Cited by 98 publications

References 20 publications

Inhibition of Human Tumor-Infiltrating Lymphocyte Effector Functions by the Homophilic Carcinoembryonic Cell Adhesion Molecule 1 Interactions

Inhibition of Human Tumor-Infiltrating Lymphocyte Effector Functions by the Homophilic Carcinoembryonic Cell Adhesion Molecule 1 Interactions

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

CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases

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