Caveolin-1 expression is elevated in claudin-low mammary tumor cells

Thompson, Devan E; Siwicky, Megan D.; Moorehead, Roger A.

doi:10.1186/1475-2867-12-6

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…To determine whether the tumor cells themselves were producing OPN, cell lines derived from different MTB-IGFIR mammary tumors were evaluated. The two best characterized lines are RJ345 cells (which have characteristics similar to PMT tumors in MTB-IGFIR transgenic mice) and RJ348 cells (which have characteristics similar to RST tumors in MTB-IGFIR transgenic mice) [ 34 , 38 – 40 ]. As shown in Table 2 , RJ348 cells expressed higher levels of Spp1 than RJ345 cells.…”

Section: Resultsmentioning

confidence: 99%

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

et al. 2016

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BackgroundOsteopontin is a secreted phosphoglycoprotein that is expressed by a number of normal cells as well as a variety of tumor cells. With respect to breast cancer, osteopontin has been implicated in regulating tumor cell proliferation and migration/metastasis and may serve as a prognostic indicator. However it remains unclear whether osteopontin has the same impact in all breast cancer subtypes and in particular, osteopontin’s effects in claudin-low breast cancer are poorly understood.MethodscDNA microarrays and qRT-PCR were used to evaluate osteopontin expression in mammary tumors from MTB-IGFIR transgenic mice and cell lines derived from these tumors. siRNA was then used to determine the impact of osteopontin knockdown on proliferation, apoptosis and migration in vitro in two murine claudin-low cell lines as well as identify the receptor mediating osteopontin’s physiologic effects.ResultsOsteopontin was expressed at high levels in mammary tumors derived from MTB-IGFIR transgenic mice compared to normal mammary tissue. Evaluation of cell lines derived from different mammary tumors revealed that mammary tumor cells with claudin-low characteristic expressed high levels of osteopontin whereas mammary tumor cells with mixed luminal and basal-like features expressed lower levels of osteopontin. Reduction of osteopontin levels using siRNA significantly reduced proliferation and migration while increasing apoptosis in the claudin-low cell lines. Osteopontin’s effect appear to be mediated through a receptor containing ITGAV and not through CD44.ConclusionsOur data suggests that mammary tumors with a mixed luminal/basal-like phenotype express high levels of osteopontin however this osteopontin appears to be largely produced by non-tumor cells in the tumor microenvironment. In contrast tumor cells with claudin-low characteristics express high levels of osteopontin and a reduction of osteopontin in these cells impaired proliferation, survival and migration.

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Section: Resultsmentioning

confidence: 99%

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

et al. 2016

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“…While its prognostic role is unclear, in a comprehensive meta-analysis, the epithelial expression of CAV-1 showed significant positive correlations with the clinical characteristics of triple negativity and positivity for cytokeratin 5/6 [ 17 ]. More recently, overexpression of CAV-1 was observed in the claudin-low mesenchymal subtype of breast cancer cells in murine models, implicating it as a possible biomarker for this challenging subgroup [ 18 ]. However, these observations have not been clearly supported by biologic studies in any triple-negative breast cancer model.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms

et al. 2016

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PurposeCaveolin-1 (CAV-1) expression is more associated with basal-like cancers than estrogen receptor- or ErbB-2–expressing breast cancers. However, the biological relevance of different levels of CAV-1 expression according to subtype in the epithelial compartment of breast cancer remains unclear.Materials and MethodsWe investigated whether CAV-1 functions as a tumor suppressor and/or modulator of the cytotoxic activity of docetaxel (DTX) in subtypes of breast cancer using in vitro and xenograft models.ResultsThe levels of CAV-1 expression were closely associated with DTX sensitivity in triple-negative breast cancer cells. In addition, CAV-1 significantly inhibited cell proliferation and modulated DTX-induced apoptosis through cell cycle arrest in the G2/M phase. The mechanisms underlying DTX-induced apoptosis differed in breast cancers according to the levels of CAV-1 expression. DTX robustly enhanced Bcl-2 inactivation by CAV-1 in MDA-MB-231 cells, while p53-mediated cell cycle arrest by DTX was more pronounced in CAV-1–low but p53-functional MCF-7 cells. In parallel with the data from breast cancer cell lines, CAV-1–transfected MCF-7 cells showed higher efficacy of DTX treatment in a xenograft model.ConclusionWe clearly demonstrated cooperative effects between CAV-1 and DTX in mediating apoptosis, suggesting that the levels of CAV-1 expression might be an important indicator for DTX use in breast cancer.

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“…Compared with other subtypes of breast cancer, CLBC has high expression of EMT-related markers (such as Vimentin, SNAI1 and SNAI2, TWIST1 and TWIST2, and ZEB1 and ZEB2) ( 114 ) and breast cancer stem cells/tumors with the initial cell markers ALDH1 and CD44 hi/ CD24 -/low ( 115 , 117 ) and high expression of PD-L1 ( 122 ). Recently, caveolin-1, galectin-1, and SMYD3 were found to be highly expressed in CLBC ( 123 – 125 ).…”

Section: Clinicopathological Characteristics Of Claudin-low Breast Ca...mentioning

confidence: 99%

Research progress of Claudin-low breast cancer

Pan,

Xu,

et al. 2023

Front. Oncol.

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Claudin-low breast cancer (CLBC) is a subgroup of breast cancer discovered at the molecular level in 2007. Claudin is one of the primary proteins that make up tight junctions, and it plays crucial roles in anti-inflammatory and antitumor responses as well as the maintenance of water and electrolyte balance. Decreased expression of claudin results in the disruption of tight junction structures and the activation of downstream signaling pathways, which can lead to tumor formation. The origin of Claudin-low breast cancer is still in dispute. Claudin-low breast cancer is characterized by low expression of Claudin3, 4, 7, E-cadherin, and HER2 and high expression of Vimentin, Snai 1/2, Twist 1/2, Zeb 1/2, and ALDH1, as well as stem cell characteristics. The clinical onset of claudin-low breast cancer is at menopause age, and its histological grade is higher. This subtype of breast cancer is more likely to spread to lymph nodes than other subtypes. Claudin-low breast cancer is frequently accompanied by increased invasiveness and a poor prognosis. According to a clinical retrospective analysis, claudin-low breast cancer can achieve low pathological complete remission. At present, although several therapeutic targets of claudin-low breast cancer have been identified, the effective treatment remains in basic research stages, and no animal studies or clinical trials have been designed. The origin, molecular biological characteristics, pathological characteristics, treatment, and prognosis of CLBC are extensively discussed in this article. This will contribute to a comprehensive understanding of CLBC and serve as the foundation for the individualization of breast cancer treatment.

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Caveolin-1 expression is elevated in claudin-low mammary tumor cells

Cited by 5 publications

References 38 publications

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms

Research progress of Claudin-low breast cancer

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