Journal ArticleDOI
Prognostic significance of tumor/stromal caveolin‐1 expression in breast cancer patients
Nian-Song Qian,Takayuki Ueno,Nobuko Kawaguchi-Sakita,Masahiro Kawashima,Noriyuki Yoshida,Yoshiki Mikami,Tomoko Wakasa,Masayuki Shintaku,Shigeru Tsuyuki,Takashi Inamoto,Masakazu Toi +10 more
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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.read more
Citations
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Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: Visualizing the therapeutic effects of metformin in tumor tissue
Diana Whitaker-Menezes,Ubaldo E. Martinez-Outschoorn,Neal Flomenberg,Ruth Birbe,Agnieszka K. Witkiewicz,Anthony Howell,Stephanos Pavlides,Aristotelis Tsirigos,Adam Ertel,Richard G. Pestell,Paolo Broda,Carlo Minetti,Michael P. Lisanti,Michael P. Lisanti,Michael P. Lisanti,Federica Sotgia,Federica Sotgia,Federica Sotgia +17 more
TL;DR: These data provide the first functional in vivo evidence that epithelial cancer cells perform enhanced mitochondrial oxidative phosphorylation, allowing them to produce high amounts of ATP, and believe that mitochondria are both the “powerhouse” and “Achilles’ heel” of cancer cells.
Journal ArticleDOI
Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis.
Stephanos Pavlides,Iset Medina Vera,Ricardo Gandara,Sharon Sneddon,Richard G. Pestell,Isabelle Mercier,Ubaldo E. Martinez-Outschoorn,Diana Whitaker-Menezes,Anthony Howell,Federica Sotgia,Michael P. Lisanti +10 more
TL;DR: A new two-compartment model for understanding tumor metabolism is proposed, which adds a novel stromal twist to two very well-established cancer paradigms: aerobic glycolysis and autophagy.
Journal ArticleDOI
Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors.
Ubaldo E. Martinez-Outschoorn,Zhao Lin,Casey Trimmer,Neal Flomenberg,Chenguang Wang,Stephanos Pavlides,Richard G. Pestell,Anthony Howell,Federica Sotgia,Michael P. Lisanti +9 more
TL;DR: In this article, the reverse Warburg effect was used to show that cancer cells initially secrete hydrogen peroxide that then triggers oxidative stress in neighboring fibroblasts, which is propagated laterally and vectorially from cancer cells to adjacent stromal cells.
Journal ArticleDOI
Using the “reverse Warburg effect” to identify high-risk breast cancer patients: Stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers
Agnieszka K. Witkiewicz,Diana Whitaker-Menezes,Abhijit Dasgupta,Nancy J. Philp,Zhao Lin,Ricardo Gandara,Sharon Sneddon,Ubaldo E. Martinez-Outschoorn,Federica Sotgia,Federica Sotgia,Michael P. Lisanti,Michael P. Lisanti +11 more
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.
Journal ArticleDOI
Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs "fertilizer".
Michael P. Lisanti,Ubaldo E. Martinez-Outschoorn,Zhao Lin,Stephanos Pavlides,Diana Whitaker-Menezes,Richard G. Pestell,Anthony Howell,Federica Sotgia +7 more
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
Cancer-associated fibroblasts and tumor growth--bystanders turning into key players.
Arne Östman,Martin Augsten +1 more
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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