Activated Leukocyte Cell Adhesion Molecule Expression Is Up-Regulated in the Development of Endometrioid Carcinoma

Liang, Shu‐Chuan; Huang, Cuiping; Jia, Shasha; Wang, Bo

doi:10.1097/igc.0b013e31820e135a

Cited by 9 publications

(8 citation statements)

References 23 publications

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“…The possible use of sALCAM as biomarker in ovarian cancer is still to be addressed by comparisons with other gynecological diseases. In this context a recent study showed upregulation of ALCAM mRNA in endometrial carcinoma, although no data on sALCAM levels were provided 44…”

Section: Discussionmentioning

confidence: 98%

Activated leukocyte cell adhesion molecule soluble form: a potential biomarker of epithelial ovarian cancer is increased in type II tumors

Carbotti

Orengo

Mezzanzanica

et al. 2012

Intl Journal of Cancer

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Activated leukocyte cell adhesion molecule (ALCAM) is involved in cell-cell interactions in cancer. Shedding of its ectodomain by the metalloprotease ADAM17/TACE generates a soluble form (sALCAM). Here, we show that serum sALCAM levels were significantly higher in epithelial ovarian cancer (EOC) (p < 0.005) than in controls. The performance of sALCAM as classifier, tested by receiver operating characteristic curve, resulted in an area under the curve (AUC) of 0.8067. Serum sALCAM levels showed direct correlation with Carbohydrate Antigen-125 (CA125/MUC16). Moreover, significantly higher levels were found in type II tumors, even in stage I/II, suggesting that elevated sALCAM is an early feature of aggressive EOC. In addition, sALCAM levels were higher in ascites than in sera, suggesting local processing of ALCAM in the peritoneal cavity. In immunodeficient mice, intraperitoneally implanted with a human EOC cell line, human sALCAM progressively increased in serum and was even higher in the ascites. The biochemical characterization of the sALCAM in EOC sera and ascites, showed two predominant forms of approximately 95 and 65 kDa but no EOC-specific isoform. In addition, full-length transmembrane ALCAM but no soluble form was detected in tumor-derived exosomes found in ascites. Finally, in vitro invasion assays showed that inhibition of ADAM17/TACE activity decreased EOC invasive properties, while opposite effects were mediated by a sALCAM-Fc chimera and by an antibody interfering with ALCAM/ALCAM interactions. Altogether these data suggest that sALCAM is a marker of EOC, which correlates with more aggressive type II tumors, and that ADAM17/TACE activity and sALCAM itself mediate enhanced invasiveness.

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Section: Discussionmentioning

confidence: 98%

Activated leukocyte cell adhesion molecule soluble form: a potential biomarker of epithelial ovarian cancer is increased in type II tumors

Carbotti

Orengo

Mezzanzanica

et al. 2012

Intl Journal of Cancer

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“…Although ALCAM has been implicated in these numerous pathological states, it is as yet unclear how ALCAM contributes to metastasis. Existing reports are paradoxical, with ALCAM gene expression being highly upregulated in some cancers [25], [31], [34] and greatly downregulated in others [28], [35], [36]. Unfortunately, these data are necessarily correlative in nature; therefore, an understanding of the contribution of ALCAM to cancer progression and, indeed, normal cell motility and adhesion, has been hampered by a lack of studies aimed at directly manipulating ALCAM levels within particular cell lines and determining the outcome of this manipulation.…”

Section: Introductionmentioning

confidence: 99%

ALCAM Regulates Motility, Invasiveness, and Adherens Junction Formation in Uveal Melanoma Cells

2012

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ALCAM, a member of the immunoglobulin superfamily, has been implicated in numerous developmental events and has been repeatedly identified as a marker for cancer metastasis. Previous studies addressing ALCAM’s role in cancer have, however, yielded conflicting results. Depending on the tumor cell type, ALCAM expression has been reported to be both positively and negatively correlated with cancer progression and metastasis in the literature. To better understand how ALCAM might regulate cancer cell behavior, we utilized a panel of defined uveal melanoma cell lines with high or low ALCAM levels, and directly tested the effects of manipulating these levels on cell motility, invasiveness, and adhesion using multiple assays. ALCAM expression was stably silenced by shRNA knockdown in a high-ALCAM cell line (MUM-2B); the resulting cells displayed reduced motility in gap-closure assays and a reduction in invasiveness as measured by a transwell migration assay. Immunostaining revealed that the silenced cells were defective in the formation of adherens junctions, at which ALCAM colocalizes with N-cadherin and ß-catenin in native cells. Additionally, we stably overexpressed ALCAM in a low-ALCAM cell line (MUM-2C); intriguingly, these cells did not exhibit any increase in motility or invasiveness, indicating that ALCAM is necessary but not sufficient to promote metastasis-associated cell behaviors. In these ALCAM-overexpressing cells, however, recruitment of ß-catenin and N-cadherin to adherens junctions was enhanced. These data confirm a previously suggested role for ALCAM in the regulation of adherens junctions, and also suggest a mechanism by which ALCAM might differentially enhance or decrease invasiveness, depending on the type of cadherin adhesion complexes present in tissues surrounding the primary tumor, and on the cadherin status of the tumor cells themselves.

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“…In order to identify an optimal target for NIRF imaging of xenograft models, selected cell surface proteins (EpCAM, activated leukocyte cell adhesion molecule (ALCAM), insulin-like growth factor 1 receptor alpha (IGF1R), and L1 cell adhesion molecule (L1CAM)) reported to be expressed in endometrial carcinoma [26][27][28][29][30][31][32][33] were screened by flow cytometry in the endometrial carcinoma cell line Ishikawa. EpCAM was found to have the highest expression, with positive staining in 99.9% of cells and a mean fluorescent intensity (MFI) fold increase of 305.3 in comparison to unstained cells ( Figure 1A, Table S1).…”

Section: Endometrial Carcinoma Cell Lines Express Epcam In Vitromentioning

confidence: 99%

“…To identify potential target molecules for NIRF imaging, databases (www.proteinatlas.org and www.uniprot.org) were searched for proteins located on the surface of endometrial carcinoma cells. Candidate proteins with reported overexpression in endometrial carcinoma compared to normal epithelium (ALCAM, EpCAM and IGF1Rα) or with positive expression associated with aggressive disease (L1CAM) were selected [26,[28][29][30][31][32][33]. Direct PE-conjugated monoclonal antibodies (Mouse Anti-EpCAM PE (clone EBA-1), PE Mouse Anti-Human CD221 (clone 1H7), PE Mouse Anti-Human CD166 (clone 3A6) (all BD Biosciences, San Jose, CA, USA) and Mouse Anti-Human CD171 Antibody (PE) (clone 03, Sino Biological Inc., Beijing, China) were purchased and tested by flow cytometry to evaluate target expression in cell lines.…”

Section: Monoclonal Antibodies For In Vitro Studiesmentioning

confidence: 99%

Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models

Fonnes

Strand

Fasmer

et al. 2020

Cancers

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Imaging of clinically relevant preclinical animal models is critical to the development of personalized therapeutic strategies for endometrial carcinoma. Although orthotopic patient-derived xenografts (PDXs) reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by the lack of appropriate imaging modalities. Here, we describe molecular imaging of a near-infrared fluorescently labeled monoclonal antibody targeting epithelial cell adhesion molecule (EpCAM) as an in vivo imaging modality for visualization of orthotopic endometrial carcinoma PDX. Application of this near-infrared probe (EpCAM-AF680) enabled both spatio-temporal visualization of development and longitudinal therapy monitoring of orthotopic PDX. Notably, EpCAM-AF680 facilitated imaging of multiple PDX models representing different subtypes of the disease. Thus, the combined implementation of EpCAM-AF680 and orthotopic PDX models creates a state-of-the-art preclinical platform for identification and validation of new targeted therapies and corresponding response predicting markers for endometrial carcinoma.

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Activated Leukocyte Cell Adhesion Molecule Expression Is Up-Regulated in the Development of Endometrioid Carcinoma

Abstract: The up-regulation of ALCAM expression during endometrial carcinogenesis and the correlations of ALCAM expression with grade and myometrial invasion suggest its potential role as a diagnostic and prognostic biomarker.

Cited by 9 publications

References 23 publications

Activated leukocyte cell adhesion molecule soluble form: a potential biomarker of epithelial ovarian cancer is increased in type II tumors

Activated leukocyte cell adhesion molecule soluble form: a potential biomarker of epithelial ovarian cancer is increased in type II tumors

ALCAM Regulates Motility, Invasiveness, and Adherens Junction Formation in Uveal Melanoma Cells

Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models

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