396 GLUT1 and CAIX expression profiles in breast cancer correlate with MCT1 overexpression

Pinheiro, Céline; Sousa, Bárbara; Albergaria, André; Paredes, Jesús; Düfloth, Rozany Mucha; Vieira, Dioracy Fonterrada; Schmitt, Fernando; Baltazar, F.

doi:10.1016/s1359-6349(10)71197-6

Cited by 44 publications

(56 citation statements)

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“…This enhanced MCT1 expression, as well as the expression of CD147, a MCT1/MCT4 chaperone (Kirk et al 2000, Gallagher et al 2007, was associated with basal-like-subtype tumours and other poor prognostic parameters (Pinheiro et al 2010). Additionally, we found that MCT1, but not MCT4, was associated with GLUT1 and CAIX expressions, indicating a role of MCT1 in the hyperglycolytic and acid-resistant phenotype characteristic of less oxygenated (Pinheiro et al 2011), instead of oxygenated cancer cells as pointed by others (Sonveaux et al 2008).…”

Section: Introductionsupporting

confidence: 68%

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Morais-Santos¹,

Miranda-Gonçalves²,

Pinheiro³

et al. 2013

Endocrine-Related Cancer

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The tumour microenvironment is known to be acidic due to high glycolytic rates of tumour cells. Monocarboxylate transporters (MCTs) play a role in extracellular acidification, which is widely known to be involved in tumour progression. Recently, we have described the upregulation of MCT1 in breast carcinomas and its association with poor prognostic variables. Thus, we aimed to evaluate the effect of lactate transport inhibition in human breast cancer cell lines. The effects of a-cyano-4-hydroxycinnamate, quercetin and lonidamine on cell viability, metabolism, proliferation, apoptosis, migration and invasion were assessed in a panel of different breast cancer cell lines. MCT1, MCT4 and CD147 were differently expressed among the breast cancer cell lines and, as expected, different sensitivities were observed for the three inhibitors. Interestingly, in the most sensitive cell lines, lactate transport inhibition induced a decrease in cell proliferation, migration and invasion, as well as an increase in cell death. Results were validated by silencing MCT1 expression using siRNA. The results obtained here support targeting of lactate transport as a strategy to treat breast cancer, with a special emphasis on the basal-like subtype, which so far does not have a specific molecular therapy.

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Section: Introductionsupporting

confidence: 68%

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Morais-Santos¹,

Miranda-Gonçalves²,

Pinheiro³

et al. 2013

Endocrine-Related Cancer

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“…Likewise, as GDH activity is influenced by various factors, it is presumed that GDH activity is not directly proportional to glutamine uptake by ASCT2 or GLS activity. Furthermore, basal-like type and/or TNBC has been shown to exhibit the highest glycolysis-related protein activity, including Glut1 (SLC2A1) and CAIX (CA9) (Hussein et al 2011, Pinheiro et al 2011. Taken together, the low level of GDH activity observed in TNBC in this study can be explained by its high level of glycolytic activity.…”

Section: Discussionmentioning

confidence: 49%

“…Therefore, metabolic status is also expected to differ according to molecular subtype. Previous studies support this expectation, having identified aerobic glycolysisrelated proteins such as GLUT1 (SLC2A1) and CAIX (CA9), which are highly expressed in basal-like type and/or triple-negative breast cancer (TNBC; Hussein et al 2011, Pinheiro et al 2011). However, relatively few studies have considered differences in glutamine metabolism according to the molecular subtypes of breast cancer.…”

Section: Introductionmentioning

confidence: 82%

Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer

Kim¹,

Kim

Jung

et al. 2013

Endocrine-Related Cancer

119

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The aim of this study was to investigate the expression of glutamine metabolism-related proteins to determine whether glutamine is metabolized differently according to breast cancer molecular subtype. We generated a tissue microarray of 702 breast cancer patients and performed immunohistochemical staining for glutamine metabolism-related proteins, including glutaminase 1 (GLS1 (GLS)), glutamate dehydrogenase (GDH (H6PD)), and amino acid transporter-2 (ASCT2 (SLC1A5)), which were separately evaluated in tumor and stroma compartments and then analyzed by breast cancer molecular subtypes. Breast cancers were classified as follows: 293 luminal A (41.7%), 166 luminal B (23.6%), 67 HER2 type (9.6%), and 176 TNBC (25.1%). HER2 type showed the highest stromal GLS1 (PZ0.001), tumoral GDH (PZ0.001), stromal GDH (P!0.001), and tumoral ASCT (P!0.001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer.

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“…It has been demonstrated that upregulation of glucose transporter type 1 (GLUT-1) in cancer cells is a prognostic factor in various malignancies [27]. Also, a positive correlation between the overexpression of GLUT-1 and 18 F-FDG avidity has been reported [28,29].…”

Section: Discussionmentioning

confidence: 99%

The Role of 18F-FDG PET/CT as a Prognostic Factor in Patients with Synovial Sarcoma

Chang

Lim

Park

et al. 2014

Nucl Med Mol Imaging

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Purpose This research aims to investigate the potential of 18 Ffluorodeoxyglucose positron emission tomography/computed tomography (FDG PET) to predict pathologic response after neoadjuvant chemotherapy (NAC) and overall survival (OS) of patients with synovial sarcoma in Korea. Methods Twenty patients with synovial sarcoma from January 2001 to December 2011 were reviewed retrospectively. All patients underwent pre-treatment FDG PET and tumor removal. Patients were classified with the maximum SUV (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), age, sex, histologic subtype, tumor size, NAC, resection margin, and metastasis at diagnosis. Pathologic response was assessed using the French Federation of Cancer Centers system. Statistical analyses were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards regression model, and Mann-Whitney test. Results Nine patients (45 %) showed pathologic response, and ten patients survived. Higher SUVmax, higher MTV, higher TLG, monophasic epithelial type, and metastasis at diagnosis were significantly related to poorer OS (p=0.047, 0.016, 0.016, 0.045, and 0.018, respectively). By multivariate analysis, metastasis at diagnosis was significantly related to poorer OS (p=0.012/HR=5.9, 95 % CI 1.47 to 24.1). The SUVmax, MTV, and TLG of the non-responder group were significantly higher than those of the responder group (p= 0.020, 0.020, and 0.020, respectively). There was no significant difference in size between the two groups (p=0.062). Conclusions A higher SUVmax on the pre-treatment scan, monophasic epithelial type, and metastasis at diagnosis were significantly associated with a poorer OS, and pathologic responders showed a higher SUVmax before NAC. The PET parameters can be used to predict OS and pathologic response in patients with synovial sarcomas before NAC.

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396 GLUT1 and CAIX expression profiles in breast cancer correlate with MCT1 overexpression

Cited by 44 publications

References 0 publications

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer

The Role of 18F-FDG PET/CT as a Prognostic Factor in Patients with Synovial Sarcoma

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