Expression of VLA-4 on primary cutaneous malignant melanoma as well as P-selectin and E-selectin on intratumoral vessels correlates with clinical outcome

Schadendorf, Dirk; Heidel, J; Gawlik, Christian; Suter, L.; Czarnetzki, B. M.

doi:10.1007/bf02571982

Cited by 24 publications

(30 citation statements)

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“…8,9 Moreover, the cell surface expression levels of many integrins can be directly correlated with the metastatic potential of melanoma cells. [10][11][12] Modulation of the actin cytoskeleton is critical for integrin function and tumor cell migration and invasion. 13 Changes in the actin cytoskeleton are accomplished by a variety of actin-binding proteins such as cofilin, a-actinin, filamin and plastin.…”

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confidence: 99%

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Klemke

Rafael

Wabnitz

et al. 2007

Intl Journal of Cancer

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The leukocyte specific actin-binding protein L-plastin is aberrantly expressed in several nonhematopoetic malignant tumors. However, little is known about the functional consequences of Lplastin expression. Here, we investigated the function of L-plastin in human malignant melanoma cells. Knock-down of endogenous L-plastin by siRNA treatment reduced migration of the melanoma cell line IF6. However, in melanoma patients, no correlation existed between L-plastin expression and tumor stages. This implied that additional factors such as phosphorylation of L-plastin may influence its function in tumor cells. To investigate this further, EGFP-tagged wild-type L-plastin (wt-LPL-EGFP) and a mutated, nonphosphorylatable L-plastin protein (5A7A-LPL-EGFP), were expressed in the L-plastin negative melanoma cell line MV3. Biochemical analysis revealed that wt-LPL-EGFP is phosphorylated in MV3 cells while 5A7A-LPL-EGFP is not. Although both wt-LPL-EGFP and 5A7A-LPL-EGFP were targeted to, and promote the formation of, vinculin-containing adhesion sites, static adhesion to either Matrigel or isolated extracellular matrix molecules was neither influenced by expression of wt-LPL-EGFP nor by expression of 5A7A-LPL-EGFP when compared with EGFP expressing control cells. In contrast, haptotactic, but not chemotactic, migration of melanoma cells towards either Matrigel or isolated extracellular matrix molecules was similarly enhanced, if either 5A7A-LPL-EGFP or wt-LPL-EGFP were expressed in MV3 cells. Interestingly, only cells expressing the phosphorylatable wt-LPL-EGFP protein showed enhanced invasion into Matrigel. In line with these findings the in vivo metastatic capacity of mouse B16 melanoma cells correlates with expression and phosphorylation of L-plastin. These data show that an increase in melanoma cell invasiveness requires not only expression but also phosphorylation of L-plastin. ' 2007 Wiley-Liss, Inc.Key words: migration; invasion; adhesion; L-plastin; melanoma Malignant melanoma is a very aggressive type of cancer that frequently metastasizes to distant organs. The capacity of tumor cells to form metastatic foci correlates with the ability to proteolytically degrade basement membrane barriers and to adhere to and migrate through extracellular matrix layers. 1,2 Two classes of molecules are mainly involved in these processes: the matrix metalloproteinases (MMPs) 3 and integrins. 4,5 Integrins are a large family of adhesion receptors involved in cell-cell and cellextracellular matrix interactions. They consist of heterodimers of 2 noncovalently associated a-and b-subunits. 6 The role of integrins in tumor cell metastasis has been intensively studied. 4,5,7 In human melanoma, especially b1-and b3-subunit containing integrins play important roles in metastasis, through an enhancement of adhesion, migration and invasion. 8,9 Moreover, the cell surface expression levels of many integrins can be directly correlated with the metastatic potential of melanoma cells. [10][11][12] Modulation of the actin cytoskeleton is critical f...

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confidence: 99%

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Klemke

Rafael

Wabnitz

et al. 2007

Intl Journal of Cancer

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“…Particularly, CD54 (ICAM) has been associated with melanoma progression and risk of metastasis [39]. Its expression is evident in melanoma when compared with nevi [26,[40][41][42]. The CD66 (CEA-CAM) is a glycoprotein surface molecule involved in intercellular adhesion and associated with diverse cellular functions that regulate growth and differentiation and play an important role in insulin homeostasis, vasculogenesis and immunomodulation.…”

Section: Integrins Referencementioning

confidence: 99%

Signaling Pathways Altered During the Metastatic Progression of Melanoma

Monteiro¹,

Toricelli²,

GalvonasJasiulionis³

2015

Melanoma - Current Clinical Management and Future Therapeutics

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“…The ␣ 4 ␤ 1 integrin is absent in primary and dysplastic nevi, but its expression levels increase during the transition from radial growth phase to vertical growth phase (42,43 ). Clinical studies documented a direct correlation between ␣ 4 ␤ 1 integrin expression and the occurrence of metastasis, reduced disease-free survival, and decreased overall survival (44 ). We determined that VCAM-1 was constitutively expressed on monolayers of brain and lymphatic endothelial cells and that melanoma cell adhesion to lymphatic endothelial cells was mediated by the melanoma ␣ 4 integrin binding to constitutively expressed VCAM-1 (45 ).…”

Section: The Organ Microenvironment and Brain Metastasis Endothelial mentioning

confidence: 99%

The Biology of Brain Metastasis

Langley

Fidler

2013

Clinical Chemistry

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BACKGROUND:It is estimated that at least 200 000 cases of brain metastases occur each year in the US, which is 10 times the number of patients diagnosed with primary brain tumors. Brain metastasis is associated with poor prognosis, neurological deterioration, diminished quality of life, and extremely short survival. Favorable interactions between tumor cells and cerebral microvascular endothelial cells encourage tumor growth in the central nervous system, while tumor cell interactions with astrocytes protect brain metastases from the cytotoxic effects of chemotherapy. CONTENT:We review the pathogenesis of brain metastasis and emphasize the contributions of microvascular endothelial cells and astrocytes to disease progression and therapeutic resistance. Animal models used to study brain metastasis are also discussed.

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Expression of VLA-4 on primary cutaneous malignant melanoma as well as P-selectin and E-selectin on intratumoral vessels correlates with clinical outcome

Cited by 24 publications

References 0 publications

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Phosphorylation of ectopically expressed L‐plastin enhances invasiveness of human melanoma cells

Signaling Pathways Altered During the Metastatic Progression of Melanoma

The Biology of Brain Metastasis

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