Expression and activity of P-glycoprotein in transplantable hamster melanomas

Witkowski, Jacek M.; Kozłowska, K; Zarzeczna, M

doi:10.1007/s004030000146

Cited by 4 publications

(7 citation statements)

References 15 publications

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“…This is in agreement with earlier reports showing negative correlation between neoplasm progression and susceptibility to apoptosis (1,5). On the other hand, current observation of high proportion of apoptotic changes in the membranes of Ma cells is surprising in the light of our earlier reports demonstrating numerous important changes in the membranes of Ab cells compared with the melanotic line (12)(13)(14). It is possible that these phenotypical changes in the plasma membranes of Ab cells may reflect functional changes in the phenotypically altered cells, leading to the expansion of the neoplasm and prevention of apoptotic death.…”

Section: Discussionsupporting

confidence: 92%

“…Our group has been studying for many years the properties of transplantable melanomas on the model of two related forms(lines) of hamster tumors (9–11). Despite common origin from a parental tumor, these two lines differ phenotypically with respect to the growth rate (9), antigenicity, immunogenicity (10) and numerous features in their plasma membranes (12–14). Thus, we consider them a good tool for a comparative study of spontaneous and induced apoptosis in model melanomas.…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneous Susceptibility to Spontaneous and Induced Apoptosis Characterizes Two Related Transplantable Melanomas with Different Biological Properties

Kozłowska

Cichorek

Zarzeczna

et al. 2002

Pigment Cell Research

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A family of phenotypically and biologically different transplantable hamster melanomas was derived from a single tumor more than 40 yr ago. In this work, we were seeking the differences between the abilities of the cells from two biologically heterogeneous (melanotic and amelanotic) members of this family to undergo spontaneous or camptothecin-induced apoptosis. We studied these differences by looking at three important features of the apoptotic process, i.e. binding of annexin V, DNA fragmentation and caspase-3 activity. Of these, annexin binding and DNA fragmentation were more pronounced in the parental, melanotic line while the activity of caspase-3 was stronger in the amelanotic tumor cells. We concluded that a spontaneous alteration of the original, melanotic melanoma line into an amelanotic one, associated with more aggressive tumor progression, was accompanied by significant decrease in ability to undergo spontaneous and camptothecin-induced apoptosis, and that apoptosis of these two cell types may not depend on the activity of caspase-3.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Heterogeneous Susceptibility to Spontaneous and Induced Apoptosis Characterizes Two Related Transplantable Melanomas with Different Biological Properties

Kozłowska

Cichorek

Zarzeczna

et al. 2002

Pigment Cell Research

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“…This effect may be mediated through activation of phosphatidylinositol 3-kinase (Yang et al, 2002). As far as melanoma is concerned, Pgp activity appeared to be associated with less differentiated and more aggressively metastasizing tumors although its role in maintaining this phenotype remains to be established (Witkowski et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The Multidrug Transporter P-Glycoprotein: A Mediator of Melanoma Invasion?

Colone

Calcabrini

Toccacieli

et al. 2008

Journal of Investigative Dermatology

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Malignant melanoma shows high levels of intrinsic drug resistance associated with a highly invasive phenotype. In this study, we investigated the role of the drug transporter P-glycoprotein (Pgp) in the invasion potential of drug-sensitive (M14 WT, Pgp-negative) and drug-resistant (M14 ADR, Pgp-positive) human melanoma cells. Coimmunoprecipitation experiments assessed the association of Pgp with the adhesion molecule CD44 in multidrug resistant (MDR) melanoma cells, compared with parental ones. In MDR cells, the two proteins colocalized in the plasma membrane as visualized by confocal microscopy and immunoelectron microscopy on ultrathin cryosections. MDR melanoma cells displayed a more invasive phenotype compared with parental cells, as demonstrated by quantitative transwell chamber invasion assay. This was accomplished by a different migration strategy adopted by resistant cells ("chain collective") previously described in tumor cells with high metastatic capacity. The Pgp molecule, after stimulation with specific antibodies, appeared to cooperate with CD44, through the activation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) proteins. This activation led to an increase of metalloproteinase (MMP-2, MMP-3, and MMP-9) mRNAs, and proteolytic activities, which are associated with an increased invasive behavior. RNA interference experiments further demonstrated Pgp involvement in migration and invasion of resistant melanoma cells. A link was identified between MDR transporter Pgp, and MAPK signaling and invasion.

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“…These melanoma lines differ in many biological features [14,15]. Pathobiological data of transplantable melanomas are presented in table 1 [17][18][19][20][21][22][23][24][25][26].…”

Section: Animals and Transplantable Melanomasmentioning

confidence: 99%

“…Expression and activity of P-glycoprotein in plasma membranes [25,26] 70% cells were Pgp positive 10% cells were Pgp positive Pgp activity stronger than Ma…”

Section: /Zarzeczna/cichorekmentioning

confidence: 99%

Sensitivity of Transplantable Melanoma Cells to Cytokines with Regard to Their Spontaneous Apoptosis

2001

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Objectives: Changes in the sensitivity of two lines of transplantable melanoma cells to the antiproliferative activity of interleukin 6 (IL-6), oncostatin M (OSM), tumor necrosis factor-α (TNF-α) during melanoma progression were the subject of this study. We were looking for a correlation between these changes and the ability of melanoma cells to undergo spontaneous apoptosis. Methods: The influence of exogenous cytokines on the proliferation of melanoma cells was measured by colorimetric methods with MTT and apoptosis of these cells was estimated by staining with annexin V/propidium iodide, measurement of DNA degradation and cell cycle analysis. Results: It was observed that during melanoma progression the sensitivity of those two melanoma line cells to the antiproliferative effect of IL-6 and OSM did not change, while a spontaneous alteration of the melanotic line into an amelanotic one seemed to be accompanied by resistance of the amelanotic melanoma cells to the antiproliferative activity of TNF-α. Simultaneously, we observed a decreased ability of amelanotic melanoma cells (in comparison with the native line) to undergo spontaneous apoptosis. Conclusions: The observed resistance to the TNF-α antiproliferative effect which appears during melanoma progression seems to be correlated with a lower ability of the amelanotic melanoma cells to undergo spontaneous apoptosis.

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Expression and activity of P-glycoprotein in transplantable hamster melanomas

Cited by 4 publications

References 15 publications

Heterogeneous Susceptibility to Spontaneous and Induced Apoptosis Characterizes Two Related Transplantable Melanomas with Different Biological Properties

Heterogeneous Susceptibility to Spontaneous and Induced Apoptosis Characterizes Two Related Transplantable Melanomas with Different Biological Properties

The Multidrug Transporter P-Glycoprotein: A Mediator of Melanoma Invasion?

Sensitivity of Transplantable Melanoma Cells to Cytokines with Regard to Their Spontaneous Apoptosis

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