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Journal ArticleDOI

Prognostic significance of tumor/stromal caveolin‐1 expression in breast cancer patients

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TLDR
The data indicate that high Cav‐1 expression in tumor cells and lack of this expression in stromal cells could help identify a particular subgroup of breast cancer patients with potentially poor survival.
Abstract
Caveolin-1 (Cav-1) has been extensively characterized in cancer biological research. However, the role of Cav-1 in the interaction between tumor and stromal cells remains unclear. In the present study, we examined Cav-1 expression in tumor cells and stromal cells in breast cancer tissue by immunohistochemical analysis and evaluated its prognostic value in a training cohort. Immunohistochemical analysis of Cav-1 expression was scored as (++), (+) or (-) according to the proportion of positively stained tumor cells (T) and stromal cells (S). Correlation analysis between tumor/stromal Cav-1 expression and clinicopathological parameters revealed that only T(++) Cav-1 status was positively associated with tumor size and histological nodal status (P = 0.019 and 0.021, respectively). Univariate analysis revealed that combined T(++)/S(-) status was significantly correlated with unfavorable prognostic outcomes (P < 0.001). Multivariate analysis demonstrated that this combined status is an independent prognostic factor for primary breast cancer (P = 0.002). Clinical outcomes in different subgroups of breast cancer patients were also strictly dependent on this combined status (P < 0.05). The prognostic value of T(++)/S(-) Cav-1 status was also validated in the testing cohort. Collectively, our data indicate that high Cav-1 expression in tumor cells and lack of this expression in stromal cells could help identify a particular subgroup of breast cancer patients with potentially poor survival. Further studies are required to understand the regulatory mechanism of Cav-1 in the tumor microenvironment.

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Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: Visualizing the therapeutic effects of metformin in tumor tissue

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Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors.

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Using the “reverse Warburg effect” to identify high-risk breast cancer patients: Stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers

TL;DR: The “Reverse Warburg Effect” or “parasitic” energy-transfer is a key determinant of poor overall patient survival and MCT4 inhibitors should be developed for the treatment of aggressive breast cancers, and possibly other types of human cancers.
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Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs "fertilizer".

TL;DR: Using various therapeutic strategies (such as catalase and/or other anti-oxidants) to neutralize the production of cancer-associated hydrogen peroxide, thereby preventing tumor-stroma co-evolution and metastasis is considered.
References
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Journal ArticleDOI

Role of Caveolae and Caveolins in Health and Disease

TL;DR: The mechanisms by which caveolae and caveolins participate in human disease processes are provided, including diabetes, cancer, cardiovascular disease, atherosclerosis, pulmonary fibrosis, and a variety of degenerative muscular dystrophies.
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Interaction of a Receptor Tyrosine Kinase, EGF-R, with Caveolins: CAVEOLIN BINDING NEGATIVELY REGULATES TYROSINE AND SERINE/THREONINE KINASE ACTIVITIES *

TL;DR: The direct interaction of caveolin with a growth factor receptor, EGF-R, a known caveolae-associated receptor tyrosine kinase is reported, suggesting that caveolin may function as a general kinase inhibitor.
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Triple-negative breast cancer—current status and future directions

TL;DR: Triple-negative breast cancer is defined by a lack of expression of both estrogen and progesterone receptor as well as human epidermal growth factor receptor 2, characterized by distinct molecular, histological and clinical features including a particularly unfavorable prognosis despite increased sensitivity to standard cytotoxic chemotherapy regimens.
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Multiple Functions of Caveolin-1

TL;DR: Caveolin-1 is an unusual protein that can be both an integral membrane protein and soluble in multiple cellular compartments and this property is an important clue about its function.
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Cancer-associated fibroblasts and tumor growth--bystanders turning into key players.

TL;DR: Clinical studies aiming at CAF-targeting can now be envisioned based on findings from experimental intervention studies with agents targeting, for example FAP or PDGF-, TGF-beta- or hedgehog-signaling.
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