A secreted form of P-cadherin is expressed in malignant melanoma

Bauer, Robert; Hein, Rüdiger; Bosserhoff, Anja‐Katrin

doi:10.1016/j.yexcr.2005.01.024

Cited by 23 publications

(23 citation statements)

References 36 publications

(44 reference statements)

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“…13 Protein analyses of melanoma tissue samples and immunohistochemistry of a small group of primary and metastatic melanoma tissue verified the expression of this short form of P-cadherin in situ as well. Furthermore, analysis showed that this short 50-kDa form of P-cadherin is secreted by melanoma cells in contrast with the membrane-bound form in melanocytes.…”

mentioning

confidence: 84%

“…13 In brief, tissues were deparaffinised, rehydrated and subsequently incubated with primary polyclonal P-cadherin-antibody (1:100; BD Bioscience Franklin Lakes, USA) or anti-Ki-67 (rabbit monoclonal, clone MIB1; Dako Cytomation GmbH, Hamburg, Germany; 1:10, final concentration 5 mg/ml) overnight at 4˚C. The secondary antibody supplied with the kit was incubated for 30 min at room temperature.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

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Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays

Bauer

Wild²,

Meyer³

et al. 2006

J Clin Pathol

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mentioning

confidence: 84%

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays

Bauer

Wild²,

Meyer³

et al. 2006

J Clin Pathol

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“…The fibroblastic population also becomes activated, which results in increased growth factor production leading to a hyperproliferative microennvironment that supports growth of many cell types. intracellular signals responsible for an assortment of cellular processes including survival, migration, invasion, and proliferation [Bauer et al, 2005]. Upon binding to the appropriate extracellular matrix (ECM) component, integrins form focal adhesions which contain clusters of signaling molecules that mediate the above-described processes.…”

Section: Melanocytes and Melanoma Cellsmentioning

confidence: 99%

Microenvironmental influences in melanoma progression

Lee

Herlyn

2006

J of Cellular Biochemistry

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An often overlooked facet of tumor biology research is the involvement of the surrounding tumor microenvironment. Increasing evidence is being presented to support a major role for stromal components in all stages of tumorigenesis including initiation, progression, and metastasis. Melanoma serves as a model for studying cellular and stromal interactions within the tumor microenvironment due to the array of cell types localized to these lesions. Here, we discuss the both the molecular mechanisms, as well as the extracellular and contextual input that contribute to melanoma progression. Special emphasis is given to the assorted cell types and their interactions with the extracellular matrix and adjacent cells. Melanoma progression also initiates development of intralesional hypoxic regions; the relative significance of hypoxia in disease is also addressed. Lastly, a number of laboratories are currently developing innovative strategies to study melanoma within a microenvironmental platform. These promising model systems and their potential for closing current gaps in knowledge of disease are reviewed. The development of such models holds translational value that cannot be achieved with most current systems.

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“…The same antiinvasive effect of P-cadherin was seen in lung carcinoma, in contrast to breast and pancreas carcinomas where P-cadherin stimulates invasion (Foty and Steinberg, 1997;Paredes et al, 2004;Taniuchi et al, 2005). The role of P-cadherin, either as invasion-promotor or as invasionsuppressor, and associated factors have been studied most extensively in breast cancer and melanoma, both in patient samples and in cell lines (Sanders et al, 1999;Paredes et al, 2004;Bachmann et al, 2005;Bauer et al, 2005;Van Marck et al, 2005;Albergaria et al, 2010;Jacobs et al, 2010). Besides the anti-invasive effect of P-cadherin in melanoma cells in vitro, the cytoplasmic expression of P-cadherin in melanoma sections could be associated with increased tumor thickness, level of invasion, and reduced overall survival (Bachmann et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Besides the anti-invasive effect of P-cadherin in melanoma cells in vitro, the cytoplasmic expression of P-cadherin in melanoma sections could be associated with increased tumor thickness, level of invasion, and reduced overall survival (Bachmann et al, 2005). Moreover, a truncated variant of P-cadherin, lacking the transmembrane and cytoplasmic region, has been shown to be expressed in melanoma cells, probably blocking the interaction between adjacent cells, thereby facilitating invasion and metastasis (Bauer et al, 2005). As shown by Sanders et al (1999), the most significant change in cadherin expression profile occurs at the stage of metastasis of vertical growth phase melanoma characterized by loss and derangement of membranous P-cadherin.…”

Section: Introductionmentioning

confidence: 99%

P-cadherin expression reduces melanoma growth, invasion, and responsiveness to growth factors in nude mice

Jacobs

Feys

Vanhoecke

et al. 2011

European Journal of Cancer Prevention

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The prognostic discrepancy between localized melanoma and metastatic disease demands a better understanding of melanoma progression. The role of E-cadherin and N-cadherin in melanoma has been widely studied; however, the function of P-cadherin remains to be elucidated. We wanted to assess the effects of P-cadherin overexpression in BLM melanoma cells with regard to xenograft growth, invasion, and survival of mice in our model to mimic micrometastatic spread. Swiss nu/nu mice were subcutaneously injected with control (BLM LIE) and P-cadherin overexpressing (BLM P-cad) melanoma cells alone and in combination with myofibroblasts, and intracardially injected with BLM LIE and BLM P-cad cells. Tumor volumes and survival of mice were assessed and analyzed. In-vitro assays were used to further investigate the influence, and identify the target receptors of growth factors secreted by myofibroblasts in melanoma cells. In-vivo experiments point out that P-cadherin reduces xenograft growth (1621 mm ± 107 vs. 329 mm ± 71) and invasion, and prolongs overall survival (34.1 ± 0.84 vs. 51.1 ± 1.8 days) of mice in our model to mimic micrometastatic spread. Coinjection with myofibroblasts resulted in increased tumor growth in BLM LIE (3896 mm ± 64 vs. 1621 mm ± 107) in contrast to BLM P-cad (417 mm ± 47 vs. 329 ± 71). P-cadherin reduces melanoma growth and invasion, prolongs the survival of mice intracardially injected, and induces a state of decreased responsiveness to myofibroblast-derived growth factors. Therefore, P-cadherin can be considered as a potential therapeutic target in the treatment of melanoma.

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A secreted form of P-cadherin is expressed in malignant melanoma

Cited by 23 publications

References 36 publications

Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays

Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays

Microenvironmental influences in melanoma progression

P-cadherin expression reduces melanoma growth, invasion, and responsiveness to growth factors in nude mice

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