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Purpose: Caveolin is an essential constituent of caveolae and has many biological functions. Expression of caveolin-1 in cancer cells was reported to be a prognostic marker in several types of cancers, the prognostic significance of its expression in cancer-associated fibroblasts (CAFs) has not been investigated. This study aimed to evaluate the clinicopathological significance of expression by CAFs in lung adenocarcinoma. Methods: We examined caveolin-1 expression in both CAFs and cancer cells in stage I invasive lung adenocarcinoma ( n = 412) and analyzed the relationship between the expression and clinicopathological factors. Results: Caveolin-1 expression by CAFs and cancer cells was observed in 12.1% and 7.8% of adenocarcinomas, respectively. Tumors with caveolin-1-positive CAFs had vascular and pleural invasion significantly more frequently than those with caveolin-1-negative CAF ( p < 0.05). This was also the cases with tumors with caveolin-1-positive cancer cells ( p < 0.01). Caveolin-1 expression by CAFs and that by cancer cells were significant predictors of shorter recurrence-free survival ( p < 0.001). Caveolin-1 expression by CAFs and cancer cells was found in 25% and 30% of solid predominant subtype, respectively, but only 9.2% and 2.7% of non-solid predominant subtype, respectively. The frequency of cases with caveolin-1-positive CAFs or cancer cells was significantly higher in the solid predominant subtype than in non-solid predominant subtype ( p < 0.001). Conclusions: Our current results highlight the prognostic importance of caveolin-1 expression by CAFs in stage I lung adenocarcinoma and provide new insights into the biological significance of caveolin-1 in the tumor microenvironment, especially in microenvironment of solid predominant adenocarcinoma. [ABSTRACT FROM AUTHOR]

Voltage-gated potassium (Kv) channels are involved in the proliferation and transformation of mammary epithelial cells. They are thought to be related to the development of breast carcinoma, although the exact role they play in this event remains unclear. In this study, we investigated whether the expression and function of Kv channels is associated with Caveolin-1 (Cav-1, a principal component of caveolae) in different cell lines. We found that expression of Cav-1 correlated with the expression of Kv channels in mammary epithelial cells (MCF10A, MCF10A-ST1, and MCF7), and silencing of Cav-1 inhibited the expression of KCNA5 (voltage-gated shaker-related subfamily A, member 5). Immunofluorescence analysis indicated the colocalization of KCNA5 with Cav-1, whereas immunoprecipitation suggested a possible interaction between the two proteins. Overall, our finding indicated that KCNA5 protein may interact with Cav-1, thereby contributing to the proliferation and early transformation of mammary cells. [ABSTRACT FROM AUTHOR]

Excitatory amino acid transporters EAAT1 (SLC1A3), EAAT2 (SLC1A2), EAAT3 (SLC1A1), and EAAT4 (SLC1A6) serve to clear L-glutamate from the synaptic cleft and are thus important for the limitation of neuronal excitation. EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. To this end cRNA encoding EAAT1, EAAT2, EAAT3, or EAAT4 was injected into Xenopus oocytes without or with additional injection of cRNA encoding caveolin-1. The L-glutamate (2 mM)-induced inward current (I Glu) was taken as a measure of glutamate transport. As a result, I Glu was observed in EAAT1-, EAAT2-, EAAT3-, or EAAT4-expressing oocytes but not in water-injected oocytes, and was significantly decreased by coexpression of caveolin-1. Caveolin-1 decreased significantly the maximal transport rate. Treatment of EAATs-expressing oocytes with brefeldin A (5 µM) was followed by a decrease in conductance, which was similar in oocytes expressing EAAT together with caveolin-1 as in oocytes expressing EAAT1-4 alone. Thus, caveolin-1 apparently does not accelerate transporter protein retrieval from the cell membrane. In conclusion, caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. [ABSTRACT FROM AUTHOR]

The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that caveolin-1 (Cav-1) is a 22 kDa scaffolding protein and plays a pivotal role in host defense against infections and tumour suppression by reducing production of cyclin D1 and endothelial nitric oxide-synthase (eNOS). However, little is known about their roles in CRS. Therefore, we aimed to investigate the expression and role of Cav-1 in CRS. Cav-1 protein expression were investigated by immunohistochemistry method and mRNA expression of Cav-1, cyclin D1 and eNOS were assessed by real-time polymerase chain reaction in CRS and control subjects. Moreover, the effects of various stimulators with different concentrations and time on Cav-1 were evaluated on nasal explant culture. The results showed that weaker expression of Cav-1 protein and mRNA were observed in CRS, especially in CRS with nasal polyps (CRSwNP), stronger mRNA expression of cyclin D1 and eNOS were observed in CRS and Cav-1 expression was negatively related to cyclin D1 and eNOS expression, respectively. Cav-1 mRNA was augmented by IFN-γ, but supressed by IL-4 and IL-1β. In conclusion, the expression of Cav-1 was downregulated in CRS and the role of Cav-1 was impaired in CRS, especially in CRSwNP, leading to the attenuation of inhibition effect on cyclin D1 and eNOS and resulted in the overexpression of cyclin D1 and eNOS. IFN-γ may be essential for Cav-1 gene expression. [ABSTRACT FROM AUTHOR]

Caveolin-1 has a complex role in prostate cancer and has been suggested to be a potential biomarker and therapeutic target. As mature caveolin-1 resides in caveolae, invaginated lipid raft domains at the plasma membrane, caveolae have been suggested as a tumor-promoting signaling platform in prostate cancer. However, caveola formation requires both caveolin-1 and cavin-1 (also known as PTRF; polymerase I and transcript release factor). Here, we examined the expression of cavin-1 in prostate epithelia and stroma using tissue microarray including normal, non-malignant and malignant prostate tissues. We found that caveolin-1 was induced without the presence of cavin-1 in advanced prostate carcinoma, an expression pattern mirrored in the PC-3 cell line. In contrast, normal prostate epithelia expressed neither caveolin-1 nor cavin-1, while prostate stroma highly expressed both caveolin-1 and cavin-1. Utilizing PC-3 cells as a suitable model for caveolin-1-positive advanced prostate cancer, we found that cavin-1 expression in PC-3 cells inhibits anchorage-independent growth, and reduces in vivo tumor growth and metastasis in an orthotopic prostate cancer xenograft mouse model. The expression of α-smooth muscle actin in stroma along with interleukin-6 (IL-6) in cancer cells was also decreased in tumors of mice bearing PC-3-cavin-1 tumor cells. To determine whether cavin-1 acts by neutralizing caveolin-1, we expressed cavin-1 in caveolin-1-negative prostate cancer LNCaP and 22Rv1 cells. Caveolin-1 but not cavin-1 expression increased anchorage-independent growth in LNCaP and 22Rv1 cells. Cavin-1 co-expression reversed caveolin-1 effects in caveolin-1-positive LNCaP cells. Taken together, these results suggest that caveolin-1 in advanced prostate cancer is present outside of caveolae, because of the lack of cavin-1 expression. Cavin-1 expression attenuates the effects of non-caveolar caveolin-1 microdomains partly via reduced IL-6 microenvironmental function. With circulating caveolin-1 as a potential biomarker for advanced prostate cancer, identification of the molecular pathways affected by cavin-1 could provide novel therapeutic targets. [ABSTRACT FROM AUTHOR]