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Transcriptome profiles of MDA-MB-231 breast cancer cells cultured with interstitial fluids from post-mastectomy breast cancer patients

ABSTRACT: Background: While body fluids are widely used in medicine, despite the fact that interstitial fluid (IF) represents a third of our body fluid, it is the most poorly understood and under-studied. In cancer, IF pressure is elevated due to increased extracellular matrix deposition in the desmoplastic stroma surrounding tumors. However, whether IF affects cancer behavior remains unclear. Methods: We collected 180 IF using drains from patients that underwent bilateral mastectomy for unilateral breast cancer with or without immediate reconstruction. The IF were classified based on their ability to promote invasion of breast cancer cells and tested in vivo. A retrospective study linking IF-invasion score to clinical parameters was performed. Results: We observed a wide range of invasion score among IF between patients, and analysis of different IF from the same patient suggests that IF are organ-specific. Patients with high-grade tumors at diagnosis have high score IF. In mice, injections of high-score IF in a normal mammary gland promoted ductal hyperplasia, increased collagen deposition and local invasion. In a mouse model of residual disease, high-score IF increased local recurrence and promoted aggressive visceral metastases. Discussion: Exposure of normal breasts to high-score IF predisposes to the development of aggressive breast cancer long before surgery. Further, such exposure following surgery increases the risk of recurrence. Therefore, our study raises the provocative possibility that intrinsic difference in IF between individuals play an active role in the predisposition, development and clinical course of sporadic breast cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77812 | GEO | 2018/02/01

REPOSITORIES: GEO

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Project description:Background and Aims: Staging inadequately predicts metastatic risk in colon cancer patients. We used a gene expression profile derived from invasive murine colon cancer cells that were highly metastatic in an immunocompetent mouse model to identify colon cancer patients at risk for recurrence in a phase I, exploratory biomarker study. Methods: 55 colorectal cancer patients from Vanderbilt Medical Center (VMC) were used as the training dataset and 177 patients from the Moffitt Cancer Center were used as the independent dataset. The metastasis-associated gene expression profile developed from the mouse model was refined using comparative functional genomics in the VMC gene expression profiles to identify a 34-gene classifier associated with high risk of metastasis and death from colon cancer. A recurrence score derived from the biologically based classifier was tested in the Moffitt dataset. Results: A high score was significantly associated with increased risk of metastasis and death from colon cancer across all pathological stages and specifically in stage II and stage III patients. The recurrence score was shown to independently predict risk of cancer recurrence and death in both univariate and multivariate models. For example, among stage III patients, a high score translated to increased relative risk for cancer recurrence (hazard ratio = 4.7 (95% CI=1.566-14.05)). Furthermore, the recurrence score identified stage III patients whose five-year recurrence-free survival was >88% and for whom adjuvant chemotherapy did not provide improved survival. Conclusion: Our biologically based gene expression profile yielded a potentially useful classifier to predict cancer recurrence and death independently of conventional measures in colon cancer patients. Experiment Overall Design: Gene expression array differences between highly invasive mouse colon cancer cells and non-invasive colon cancer cells were used to develop a metastasis gene expression profile. It was refined using gene expression data from 55 patient (VMC) samples and trained using 177 patient (Moffitt) samples.

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Transcriptome profiles of MDA-MB-231 breast cancer cells cultured with interstitial fluids from post-mastectomy breast cancer patients

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