Inhibition of Metastases of a Human Melanoma Xenograft by Monoclonal Antibody to the GD2/GD3 Gangliosides

Iliopoulos, Dimitrios; Ernst, Carolyn S.; Steplewski, Zenon; Jambrosic, J.; Rodeck, Ulrich; Herlyn, Meenhard; Clark, Wallace H.; Koprowski, Hilary; Herlyn, Dorothee

doi:10.1093/jnci/81.6.440

Cited by 78 publications

(41 citation statements)

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“…The facts that GD3 is highly expressed in melanomas in comparison with melanocytes, is exclusively expressed in the early developmental stage of the fetal brain (10), and is highly expressed in activated T lymphocytes and in T cell malignant tumor cells (12)(13)(14)(15) suggest that GD3 is involved in tumor phenotypes, such as enhanced proliferation and frequent metastasis. There have been a number of reports indicating that GD3 is associated with cell adhesion to the extracellular matrix (20), increased cell growth (17), and invasion activity (21). In fact, anti-GD3 antibodies appeared to suppress cultured melanoma growth (16,22), and GD3-lacking mutants of SK-MEL-28 showed markedly reduced cell proliferation (17), supporting its role in cell growth.…”

Section: Discussionmentioning

confidence: 98%

Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells

Hamamura

Hayashi²,

Hattori³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

146

163

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Although ganglioside GD3 levels are highly elevated in malignant melanomas, the role of GD3 in melanomas' malignant properties has not been clearly shown. To investigate this problem, we genetically generated GD3-positive (GD3 ؉ ) transfectant cells from a GD3-negative (GD3 ؊ ) mutant line SK-MEL-28-N1 and analyzed the phenotypic changes in the transfected cells. GD3 ؉ cells showed markedly increased cell growth and invasive characteristics. Two bands that underwent stronger tyrosine phosphorylation in GD3 ؉ cell lines than in controls after treatment with FCS were found with molecular masses of 130 and 68 kDa. They were identified as p130Cas and paxillin by sequential immunoprecipitation. Their roles in cell growth and invasion were analyzed with a small interfering RNA (siRNA) approach. Cell growth, as analyzed by BrdUrd uptake, was strongly suppressed in GD3 ؉ cells to near the levels of GD3 ؊ cells when treated with siRNA for p130Cas but not when treated with siRNA for paxillin. However, treatment with siRNAs of either p130Cas or paxillin resulted in the marked suppression of the invasive activity of GD3 ؉ cells almost to the levels of control cells. These results suggested that these two molecules function as effectors of GD3-mediated signaling, leading to such malignant properties as rapid cell growth and invasion.small interfering RNA ͉ sialyltransferase ͉ phosphorylation

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Section: Discussionmentioning

confidence: 98%

Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells

Hamamura

Hayashi²,

Hattori³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

146

163

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“…Neutrophils express several subtypes of FcRs capable of inducing ADCC, including FcγRI (CD64), FcγRIIa (CD32), FcγRIIIa (CD16a), and FcγRIIIb (CD16b) [336][337][338], whose surface expression is increased following G-CSF stimulation [338,339]. FcγRI was shown to mediate neutrophil ADCC activity against glioma, squamous cell and ovarian carcinoma cells [338].…”

Section: Antibody-dependent Cell-mediated Cytotoxicity (Adcc)mentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

342

261

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Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation.

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“…mRNA levels of MMP-2 were exceptionally high in some melanoma cell lines (WM239, WM793, WM852 and WM165), while in three other melanoma cell lines (G361, WM164, Bowes) MMP-2 was expressed at a level comparable to that of HT-1080 cells (Figure 3). Interestingly, the cell lines G361 and WM164, that were negative for both MMP-1 and -2 mRNAs, have been established from primary non-metastatic melanoma cell lines (Peebles et al, 1980;Iliopoulos et al, 1989). Cell lines expressing both MMP-1 and -2 (WM239, WM165, ML852) have been established from melanoma metastases (Herlyn et al, 1985a(Herlyn et al, , 1985b.…”

Section: Mt1-mmp and Mmp-2 Are Expressed By Cultured Melanoma Cellsmentioning

confidence: 99%

Expression of collagenases-1 and -3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas

et al. 1999

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Summary Since proteolysis of the dermal collagenous matrix and basement membranes is required for local invasive growth and early metastasis formation of cutaneous melanomas, we have analysed the activities/expression levels of certain metalloproteinases in melanomas and cultured melanoma cells by in situ hybridization and Northern analysis. In addition to collagenases-1 and -3 that have been implicated in invasive growth behaviour of various malignant tumours, we analysed the levels of 72-kDa gelatinase and its activators MT1-MMP and TIMP-2 in cultured melanoma cells. The lesions examined included three cases of lentigo maligna and 28 cases of Clark grade I-V melanomas. The premalignant as well as the grade I tumours were consistently negative for collagenase-1 and -3 and TIMP-1 and -3. The collagenases were predominantly expressed in the cancer cells of Clark grade III and IV tumours. TIMP-1 and -3 were abundantly expressed in the cancer and/or stromal cells of grade III and IV melanomas, while TIMP-2 protein was detected also in melanomas representing lower invasive potential. Northern analysis of seven melanoma cell lines showed that the expression of collagenase-1 and TIMPs-1 and -3 was associated with 72-kDa gelatinase positivity. All melanoma cell lines were positive for MTI-MMP and TIMP-2 mRNAs. Our results suggest that overexpression of collagenases-1 and -3 and TIMPs -1 and -3 is induced during melanoma progression. Expression of TIMPs may reflect host response to tumour invasion in an effort to control MMP activity and preserve extracellular matrix integrity. Keywords: MMP; cell invasion; angiogenesis; gelatinase 733British Journal of Cancer (1999) 80(5/6), 733-743 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received 10 September 1998 Revised 3 December 1998 Accepted 3 December 1998Correspondence to: UK Saarialho-Kere type I, II and III collagens. Furthermore, MMP-13 is gelatinolytic and type IV collagenolytic (Knäuper et al, 1996, and MMP-1 has also some activity against full-length type IV collagen (Collier et al, 1988). Our objective was to determine the expression patterns and cellular localization of these MMPs during melanocytic tumour progression. Furthermore, as imbalance between TIMPs and MMPs is an important factor in tumour invasion, the expression levels of collagenase inhibitors TIMP-1 and -3 were also examined. Our results suggest that the induction of MMPs-1 and -13 and their tissue inhibitors is a late event in melanocytic tumour progression, and that these enzymes are involved in the regulation of melanoma invasion. MATERIALS AND METHODS Tissue specimensFormalin-fixed, paraffin-embedded specimens were obtained from the Department of Dermatopathology, Helsinki University Central Hospital, Helsinki, Finland. Invasion levels of the melanomas were determined by Clark's classification: level I with confinement of the malignant melanoma cells to the epidermis and its appendages; level II with extension to the papillary dermis so that only a few melanoma cells extended to the int...

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Inhibition of Metastases of a Human Melanoma Xenograft by Monoclonal Antibody to the GD2/GD3 Gangliosides

Cited by 78 publications

References 0 publications

Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells

Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Expression of collagenases-1 and -3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas

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