Tissue samples from the same individual patient
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE26053 | GEO | 2011/04/07
SECONDARY ACCESSION(S): PRJNA135557
REPOSITORIES: GEO
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Project description:We searched for putative phenotypic and genotypic differences between primary lesions and melanoma metastasis. Therefore we investigated melanoma cells derived either from the primary tumor or from lymph node metastasis of the same individual patient. In vitro studies revealed high migratory and anchorage independent growth of metastasis-derived cells. Unexpectedly, whole genome DNA analysis displayed a total of 10 homozygous losses in the primum-derived cell line, whereas the metastasis–derived cell line only shared 5 of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and no growth of primum-derived cells. Therefore we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. Additionally we screened melanoma samples isolated from patients and could identify one case were the primum harboured deletions not present in the metastatic lesion. We propose that for mutation-targeted therapy genotyping should be performed not only from primary, but foremost from metastatic melanoma cells. Blood samples as well tumor samples were directly processed for DNA isolation and subsequent chip hybridization. Each sample was hybridized onto a single affymetrix SNP 6.0 chip.
2011-04-07 | E-GEOD-26053 | biostudies-arrayexpress
Project description:We searched for putative phenotypic and genotypic differences between primary lesions and melanoma metastasis. Therefore, we investigated melanoma cells derived either from the primary tumor or from lymph node metastasis of the same individual patient. In vitro studies revealed high migratory and anchorage-independent growth of metastasis-derived cells. Unexpectedly, whole genome DNA analysis displayed a total of 10 homozygous losses in the primum-derived cell line, whereas the metastasis–derived cell line only shared 5 of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and delayed growth of primum-derived cells. However, after re-grafting of primum-derived cells, tumor growth kinetic was accelerated and therefore comparable to metastasis-derived cells. Moreover, re-grafted primum-derived cells now also harboured the same reduced DNA deletion pattern, identical to human metastasis-derived cells. We conclude that our xenotransplantation model mimics clonal selection from a heterogeneous starting population, and we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. Therefore, we propose that for mutation-targeted therapy approaches, the genotyping procedure should include primary as well as metastatic melanoma biopsies.
2011-04-07 | GSE22461 | GEO
Project description:We searched for putative phenotypic and genotypic differences between primary lesions and melanoma metastasis. Therefore, we investigated melanoma cells derived either from the primary tumor or from lymph node metastasis of the same individual patient. In vitro studies revealed high migratory and anchorage-independent growth of metastasis-derived cells. Unexpectedly, whole genome DNA analysis displayed a total of 10 homozygous losses in the primum-derived cell line, whereas the metastasis–derived cell line only shared 5 of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and delayed growth of primum-derived cells. However, after re-grafting of primum-derived cells, tumor growth kinetic was accelerated and therefore comparable to metastasis-derived cells. Moreover, re-grafted primum-derived cells now also harboured the same reduced DNA deletion pattern, identical to human metastasis-derived cells. We conclude that our xenotransplantation model mimics clonal selection from a heterogeneous starting population, and we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. Therefore, we propose that for mutation-targeted therapy approaches, the genotyping procedure should include primary as well as metastatic melanoma biopsies. DNA was extracted from in vitro grown cell lines, and Affymetrix SNP6.0 arrays were performed according to the manufacturer's instructions. Intensity Log2 ratios were used to manually search for homozygous deletions via the genotyping console.
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Project description:Secreted extracellular vesicles are known to influence the tumor microenvironment and promote metastasis. In this work, we have analyzed the involvement of extracellular vesicles in establishing the lymph node pre-metastatic niche by melanoma cells. We found that small extracellular vesicles (sEVs) derived from highly metastatic melanoma cell lines spread broadly through the lymphatic system and are taken up by lymphatic endothelial cells reinforcing lymph node metastasis. Melanoma-derived sEVs induce lymphangiogenesis, a hallmark of pre-metastatic niche formation, in vitro and in lymphoreporter mice in vivo. Analysis of involved factors demonstrated that the neural growth factor receptor (NGFR) is secreted in melanoma-derived small extracellular vesicles and shuttled to lymphatic endothelial cells inducing lymphangiogenesis and tumor cell adhesion through the activation of ERK and NF-B pathways and ICAM1 expression. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased melanoma lymph node metastasis and extended mice survival. Importantly, analysis of NGFR expression in lymph node metastases and matched primary tumors shows that levels of MITF+NGFR+ lymph node metastatic cells are correlated with disease outcome. Our data support that NGFR is secreted in sEVs favoring lymph node pre-metastatic niche formation and lymph node metastasis in melanoma.
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Project description:Tumor-derived exosomes are emerging as mediators of tumorigenesis with a tissue-specific address and message. We explored the function of melanoma-derived exosomes in formation of primary tumors and metastatic progression in both murine models and patients. Whereas exosomes from highly metastatic melanoma cells increased the metastatic behavior of primary tumor cells by educating bone marrow (BM) progenitor cells via the MET receptor, exosomes from low metastatic melanoma cells did not alter the incidence of metastases. Melanoma-derived exosomes induced vascular leakiness at pre-metastatic sites, and reprogrammed BM progenitor cells towards a pro-vasculogenic phenotype (c-Kit+Tie2+MET+). Reducing MET expression in tumor-derived exosomes diminished the pro-metastatic behavior of BM cells. Importantly, MET expression was upregulated in circulating BM progenitor cells (CD45-CD117low and CD45-CD117lowTIE2+) isolated from stage III and stage IV melanoma patients. Rab1a, Rab5b, Rab7, and Rab27a were highly expressed in melanoma and Rab27a RNA interference decreased exosome production and/or soluble angiogenic factors in melanoma cells, thereby preventing mobilization of BM progenitor cells, tumor growth and metastasis. Finally, we identified a melanoma signature in exosomes isolated from metastatic melanoma patients, comprised of TYRP2, VLA-4, Hsp70, an Hsp90 isoform and MET oncoprotein, which together with Rab proteins, appear to represent exosome-specific proteins with prognostic potential, and may provide new therapeutic targets. Identification of molecular finger associated to exosome effects in metastatic organs Microarray analysis of genes differentially expressed in the lungs 24 and 48 hours after B16-F10 exosome tail vein injection compared to control.
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Project description:Tumor-derived exosomes are emerging as mediators of tumorigenesis with a tissue-specific address and message. We explored the function of melanoma-derived exosomes in formation of primary tumors and metastatic progression in both murine models and patients. Whereas exosomes from highly metastatic melanoma cells increased the metastatic behavior of primary tumor cells by educating bone marrow (BM) progenitor cells via the MET receptor, exosomes from low metastatic melanoma cells did not alter the incidence of metastases. Melanoma-derived exosomes induced vascular leakiness at pre-metastatic sites, and reprogrammed BM progenitor cells towards a pro-vasculogenic phenotype (c-Kit+Tie2+MET+). Reducing MET expression in tumor-derived exosomes diminished the pro-metastatic behavior of BM cells. Importantly, MET expression was upregulated in circulating BM progenitor cells (CD45-CD117low and CD45-CD117lowTIE2+) isolated from stage III and stage IV melanoma patients. Rab1a, Rab5b, Rab7, and Rab27a were highly expressed in melanoma and Rab27a RNA interference decreased exosome production and/or soluble angiogenic factors in melanoma cells, thereby preventing mobilization of BM progenitor cells, tumor growth and metastasis. Finally, we identified a melanoma signature in exosomes isolated from metastatic melanoma patients, comprised of TYRP2, VLA-4, Hsp70, an Hsp90 isoform and MET oncoprotein, which together with Rab proteins, appear to represent exosome-specific proteins with prognostic potential, and may provide new therapeutic targets. Identification of molecular finger associated to exosome effects in metastatic organs
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