Activated leukocyte cell adhesion molecule (ALCAM/CD166): Signaling at the divide of melanoma cell clustering and cell migration?

Swart, Guido W.M.; Lunter, Pim C.; Kilsdonk, Jeroen W.J. van; Kempen, Léon C van

doi:10.1007/s10555-005-1573-0

Cited by 95 publications

(74 citation statements)

References 89 publications

(87 reference statements)

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“…In addition, focal adhesion proteins may function as a cell surface sensor to regulate cellular signaling and dynamic responses. 38 Likewise, deletion of focal adhesion kinase impairs directed migration in endothelial cells, 39 and its activation is required by both attractive and repulsive cues to control, respectively, axon outgrowth and disassembly of adhesive structures together with cytoskeletal dynamics. 40 Our model of EC invasion postulates that increased levels of ETV5 are translated into a transcriptional promotion of EMT (Figure 7a).…”

Section: Discussionmentioning

confidence: 99%

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas

et al. 2012

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Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell --cell and cell --substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.

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Section: Discussionmentioning

confidence: 99%

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas

et al. 2012

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“…Homotypic ALCAM-mediated interactions have been implicated in the onset of melanoma, because, besides the switching from E-to N-and VE-cadherin expression, ALCAM is also detected in early melanocytic transformation stages (reviewed by Swart et al, 2005). The ALCAM-positive metastatic phenotype of melanoma cells is characterized further by the absence of significant levels of the cadherins (Uhlenbrock et al, 2004;Swart et al, 2005). Fig.…”

Section: Discussionmentioning

confidence: 99%

“…ALCAM has been implicated in the onset and progression of melanoma (van Kempen et al, 2000;van Kempen et al, 2001;Lunter et al, 2005), bladder cancer (Tomita et al, 2003), prostate carcinoma (Kristiansen et al, 2003), breast cancer (King et al, 2004) and colorectal carcinoma (Weichert et al, 2004). The invasiveness of malignant melanoma correlates with enhanced ALCAM expression and this molecule is considered to be a prognostic marker in this disease (Degen et al, 1998;van Kempen et al, 2000;van Kempen et al, 2001;Swart et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Distinct kinetic and mechanical properties govern ALCAM-mediated interactions as shown by single-molecule force spectroscopy

Riet

Zimmerman

Cambi

et al. 2007

Journal of Cell Science

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The activated leukocyte cell adhesion molecule (ALCAM) mediates dynamic homotypic and heterotypic cellular interactions. Whereas homotypic ALCAM-ALCAM interactions have been implicated in the development and maintenance of tissue architecture and tumor progression, heterotypic ALCAM-CD6 interactions act to initiate and stabilize T-cell–dendritic-cell interactions affecting T-cell activation. The ability to resist the forces acting on the individual bonds during these highly dynamic cellular contacts is thought to be crucial for the (patho)physiology of ALCAM-mediated cell adhesion. Here, we used atomic force microscopy to characterize the relationship between affinity, avidity and the stability of ALCAM-mediated interactions under external loading, at the single-molecule level. Disruption of the actin cytoskeleton resulted in enhanced ALCAM binding avidity, without affecting the tensile strength of the individual bonds. Force spectroscopy revealed that the ALCAM-CD6 bond displayed a significantly higher tensile strength, a smaller reactive compliance and an up to 100-fold lower dissociation rate in the physiological force window in comparison to the homotypic interaction. These results indicate that homotypic and heterotypic ALCAM-mediated adhesion are governed by significantly distinct kinetic and mechanical properties, providing novel insight into the role of ALCAM during highly dynamic cellular interactions.

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“…CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. 11 In addition, its expression correlates with tumor thickness in primary melanoma.…”

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confidence: 99%

Increased expression of stem cell markers in malignant melanoma

et al. 2007

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The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P ¼ 0.005), CD133 (P ¼ 0.003), and nestin (P ¼ 0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P ¼ 0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P ¼ 0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.

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Activated leukocyte cell adhesion molecule (ALCAM/CD166): Signaling at the divide of melanoma cell clustering and cell migration?

Cited by 95 publications

References 89 publications

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas

Distinct kinetic and mechanical properties govern ALCAM-mediated interactions as shown by single-molecule force spectroscopy

Increased expression of stem cell markers in malignant melanoma

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