Dataset Information

Metastasis-related Intracellular Proteins in Human Breast Cancer Cells

ABSTRACT: We have used a unique metastasis model system in combination with quantitative, comparative proteomics to identify novel markers associated with the ability of cancer cells to colonize and form metastasis, and subsequently analyzed the clinical relevance of these proteins using breast cancer biopsies from patients with known clinical outcome within a 10-year follow-up. The model system consists of two isogenic human breast cancer cell lines that are equally tumorigenic in mice, but one gives rise to metastasis while the other disseminates single cells that remain dormant in distant organs. Using stable isotopic labeling by amino acids in cell culture and subcellular fractionation, the nuclear, cytosol and mitochondria proteomes were analyzed by LC-MS/MS, identifying seven proteins that exhibited altered expression between the cell lines, including L-lactate dehydrogenase A, NADH-cytochrome b5 reductase 3 (CYB5R3), niemann-pick c1 protein, and nucleolar RNA helicase 2.

INSTRUMENT(S): Waters instrument model

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Mammary Gland Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Rikke Raaen Lund

LAB HEAD: Henrik Jørn Ditzel

PROVIDER: PXD001391 | Pride | 2015-09-14

REPOSITORIES: Pride

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Publications

NADH-Cytochrome b5 Reductase 3 Promotes Colonization and Metastasis Formation and Is a Prognostic Marker of Disease-Free and Overall Survival in Estrogen Receptor-Negative Breast Cancer.

Lund Rikke R RR Leth-Larsen Rikke R Caterino Tina Di TD Terp Mikkel G MG Nissen Jeanette J Lænkholm Anne-Vibeke AV Jensen Ole N ON Ditzel Henrik J HJ

Molecular & cellular proteomics : MCP 20150908 11

Metastasis is the main cause of cancer-related deaths and remains the most significant challenge to management of the disease. Metastases are established through a complex multistep process involving intracellular signaling pathways. To gain insight to proteins central to specific steps in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using stable isotopic labeling by amino acid ...[more]

PMID: 26351264

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Project description:Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells. METHODS: We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene invasiveness gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer. RESULTS: There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response (WR) signature. CONCLUSIONS: The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer. Expression profling was performed on 6 tumorigenic, 3 non tumorigenic samples of breast tumors and 3 normal breast samples on two different platforms GPL96 and GPL97. A gene signature was derived by comparing the gene expressions of 6 tumorigenic samples with 3 normal breast samples.

Dataset Information

Metastasis-related Intracellular Proteins in Human Breast Cancer Cells

Publications

NADH-Cytochrome b5 Reductase 3 Promotes Colonization and Metastasis Formation and Is a Prognostic Marker of Disease-Free and Overall Survival in Estrogen Receptor-Negative Breast Cancer.

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