The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

Zecchini, Silvia; Bombardelli, Lorenzo; Decio, Alessandra; Bianchi, M.; Mazzarol, Giovanni; Sanguineti, F.; Aletti, Giovanni; Maddaluno, Luigi; Berezin, Vladimir; Bock, Elisabeth; Casadio, Chiara; Viale, Giuseppe; Colombo, Nicoletta; Giavazzi, Raffaella; Cavallaro, Ugo

doi:10.1002/emmm.201100152

Cited by 71 publications

(61 citation statements)

References 63 publications

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“…CD56 interaction with fibroblast growth factor receptor (FGFR) promotes ovarian cancer development, pancreatic tumor cell adhesion to the extracellular matrix, and invasiveness of epithelial tumors. [31][32][33] In addition, CD56 is involved in a variety of cell functions including cell proliferation, migration and, epithelial-mesenchymal transition. Whether CD56 expression on CRC cells has a role in the pathogenesis of CRC tumor development and is a potential marker of poor prognosis in a rare subset of CRC patient tumors remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

NK cells and T cells cooperate during the clinical course of colorectal cancer

et al. 2014

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Recent evidence suggests that natural killer (NK) cells are typically defective in infiltrating solid tumors, with the exception of gastrointestinal stromal tumors (GIST). Interestingly, however, infrequently infiltrating NK cells do not appear to have a direct effect on tumor progression. Here, prompted by the recent evidence that NK cell and T cell crosstalk may trigger, or enhance, tumor antigen-specific immune responses, we have tested the clinical significance of this reciprocal signaling. To this end, a tissue microarray constructed with 1410 colorectal carcinoma (CRC) patient specimens was stained with NK and T cell antigen-specific monoclonal antibodies, utilizing the immunoperoxidase staining technique. Cut-off scores for positive (>4 NK cells) and negative (4 NK cells) NK cell CRC patient samples were determined using receiver operating characteristic curve analysis. Using this approach, NK cells were detected in 423 (30%) of the 1410 CRC specimens evaluated. The number of NK cells was >4 in only 132 (9%) of CRC samples. Correlation of the immunohistochemical staining results together with analysis of the clinical course of the disease revealed that the infiltration of colorectal tumors with both NK cells and CD8C T cells is associated with prolonged patient survival. In contrast, infiltration of tumors with NK cells in combination with CD3C and CD4 C T lymphocytes had no detectable effect on the clinical course of the disease. These results suggest that NK cell and CD8 C T cell crosstalk in the tumor microenvironment may benefit patient outcome and further, that the enumeration of infiltrating NK and CD8 C T cells in CRC tumors may provide useful prognostic information.

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Section: Discussionmentioning

confidence: 99%

NK cells and T cells cooperate during the clinical course of colorectal cancer

et al. 2014

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“…NCAM1 stimulates migration and invasion of epithelial ovarian carcinoma cells and melanoma cells and promotes metastatic dissemination in mice. This promalignant function of NCAM1 is mediated by its interaction with fibroblast growth factor receptor (38,48). FOXG1 acts as an oncoprotein inhibiting TGF-b-mediated antiproliferative responses in medulloblastomas and ovarian cancer cells through suppressing p21 WAF1/CIP1 transcription (37,49).…”

Section: Discussionmentioning

confidence: 99%

“…We subsequently validated the microarray results by qRT-PCR of several genes, ADCY7, ARGHDIB, BAMBI, FOXG1, FSCN1, FUCA1, GFPT2, ITPR3, ITGA4, LSP1, NCAM1, NUDT14, RGS20, RHOF, and RIAM, that have already been implicated in cell migration, adhesion, or angiogenesis (28,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). The results from qRT-PCR analysis (Fig.…”

Section: Differential Gene Expression Analysis Of Pr9692shmock and Prmentioning

confidence: 99%

Downregulation of HOPX Controls Metastatic Behavior in Sarcoma Cells and Identifies Genes Associated with Metastasis

Kovářová

Plachý

Kosla

et al. 2013

Molecular Cancer Research

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Comparing the gene expression profiles of metastatic and nonmetastatic cells has the power to reveal candidate metastasis-associated genes, whose involvement in metastasis can be experimentally tested. In this study, differentially expressed genes were explored in the v-src-transformed metastatic cell line PR9692 and its nonmetastatic subclone PR9692-E9. First, the contribution of homeodomain only protein X (HOPX) in metastasis formation and development was assessed. HOPX-specific knockdown decreased HOPX expression in the nonmetastatic subclone and displayed reduced cell motility in vitro. Critically, HOPX knockdown decreased the in vivo metastatic capacity in a syngeneic animal model system. Genomic analyses identified a cadre of genes affected by HOPX knockdown that intersected significantly with genes previously found to be differentially expressed in metastatic versus nonmetastatic cells. Furthermore, 232 genes were found in both screens with at least a two-fold change in gene expression, and a number of high-confidence targets were validated for differential expression. Importantly, significant changes were demonstrated in the protein expression level of three metastaticassociated genes (NCAM, FOXG1, and ITGA4), and knockdown of one of the identified HOPX-regulated metastatic genes, ITGA4, showed marked inhibition of cell motility and metastasis formation. These data demonstrate that HOPX is a metastasis-associated gene and that its knockdown decreases the metastatic activity of v-src-transformed cells through altered gene expression patterns.

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“…With the integrins, CD44 can also be an element of binding, which attachs to hyaluronic acid [155]. Additionally, adhesion molecules such as NCAM can promote ovarian cancer metastasis via the interaction with receptors such as FGFR [156]. Proteolytic activity is a requested mechanism for cells attachment since MMP-2, at the surface of cancer cells, cleaves fibronectin and vitronectin (extracellular matrix proteins) into smaller fragments to increase adhesion, respectively, with α5β1 αvβ3 integrins [157,158].…”

Section: Specific Mechanisms Underlying Ovarian Cancer Metastasismentioning

confidence: 99%

Ovarian cancer molecular pathology

Longuespée

Boyon

Desmons

et al. 2012

Cancer Metastasis Rev

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Ovarian cancer (OVC) is the fourth leading cause of cancer mortality among women in Europe and the United States. Its early detection is difficult due to the lack of specificity of clinical symptoms. Unfortunately, late diagnosis is a major contributor to the poor survival rates for OVC, which can be attributed to the lack of specific sets of markers. Aside from patients sharing a strong family history of ovarian and breast cancer, including the BRCA1 and BRCA2 tumor suppressor genes mutations, the most used biomarker is the Cancer-antigen 125 (CA-125). CA-125 has a sensitivity of 80 % and a specificity of 97 % in epithelial cancer (stage III or IV). However, its sensitivity is 30 % in stage I cancer, as its increase is linked to several physiological phenomena and benign situations. CA-125 is particularly useful for at-risk population diagnosis and to assess response to treatment. It is clear that alone, CA-125 is inadequate as a biomarker for OVC diagnosis. There is an unmet need to identify additional biomarkers. Novel and more sensitive proteomic strategies such as MALDI mass spectrometry imaging studies are well suited to identify better markers for both diagnosis and prognosis. In the present review, we will focus on such proteomic strategies in regards to OVC signaling pathways, OVC development and escape from the immune response.

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The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

Cited by 71 publications

References 63 publications

NK cells and T cells cooperate during the clinical course of colorectal cancer

NK cells and T cells cooperate during the clinical course of colorectal cancer

Downregulation of HOPX Controls Metastatic Behavior in Sarcoma Cells and Identifies Genes Associated with Metastasis

Ovarian cancer molecular pathology

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