Expression of Cav-1 in tumour cells, rather than in stromal tissue, may promote cervical squamous cell carcinoma proliferation, and correlates with high-risk HPV infection

Abstract

Abstract. Altered expression of caveolin-1 (Cav-1) is observed in various types of cancers. However, little research has been reported regarding the correlation between the expression of Cav-1 and cervical cancer. Here, we investigated the clinical significance of Cav-1 expression using quantum dot (QD)-based immunofluorescence staining in cervical cancer and its correlation with high-risk human papilloma virus (HPV) infection detected by chromogenic in situ hybridization. Our results showed that the positive rates of Cav-1 protein in normal cervical mucosa, CIN, cervical adenocarcinoma and SCC were: 0, 33, 19 and 55%, respectively. The differences in Cav-1 protein expression in cervical SCC compared to the other three groups were all statistically significant. Absence of stromal Cav-1 protein in 58 cases of cervical SCC was 67%. The positive rates of the Cav-1 protein in tumour and stromal cells of cervical SCC were not correlated with clinicopathological parameters. In the cervical SCC tissues, Cav-1 expression in tumour cells was not associated with stromal Cav-1 expression, but a positive correlation existed with the PCNA protein and high-risk of HPV infection. The results presented here suggest that expression of Cav-1 in the tumour cells, rather than in the stromal tissue surrounding the tumour, may promote cervical SCC cell proliferation, and correlates with high-risk HPV infection. IntroductionCervical cancer is one of the most common cancer among women worldwide, and its incidence is higher in people of low socioeconomic status in developing countries, including China. It is well known that cervical carcinogenesis is caused by persistent oncogenic high-risk human papillomavirus (HR-HPV) infection (1,2). However, not all of the infected women will develop cervical cancer, still other genetic and epigenetic factors including tumour suppressor gene, oncogene, cell cycle regulating factors and apoptosis, may be involved in tumour progression (1).The caveolin (Cav) family includes Cav-1, Cav-2 and Cav-3. Cav-1 is the major structural protein of caveolae and functionally regulates the activity of many signaling molecules, which are potentially involved in the development of human cancer. Cav-1 is widely expressed in fully differentiated or quiescent cells, such as adipocytes, fibroblasts, alveolar epithelial cells, endothelial cells and smooth muscle cells. Previous studies of Cav-1 in various types of cancer showed two contrary results. On one hand, expression of Cav-1 is increased in cancer of the prostate (3), pancreas (4), breast (5), colon (6), tongue (7) and esophagus (8), thus, indicating that it plays a positive role in tumour progression. On the other hand, expression of Cav-1 is decreased in the lung (9), colon (10), ovary (11), breast (12,13), stomach (14) and thyroid cancer (15). Cav-1 has a different expression pattern across tissues in different organs, despite such tissues having the same histological type, such as squamous cell carcinomas. These data imply that Cav-1 may have multiple activiti...

Quantum Dots-Based Immunofluorescent Imaging of Stromal Fibroblasts Caveolin-1 and Light Chain 3B Expression and Identification of Their Clinical Significance in Human Gastric Cancer

“…In our study, to ensure that our results were comparable with those of the other labs, we examined the status of Cav-1 and LC3B using the developed QDs-IHC method that was well-established and widely used in quantitative and semiquantitative studies [23,43–45] rather than using the developing QDs-based multiplexed molecular imaging technology. Furthermore, results from Yan Li and colleagues [40] and the current study showed that QDs-based multiplexed molecular imaging is highly suitable for observing the heterogeneity of cancer cells and stromal cells.…”

“…Every step followed the manufacturer’s instructions (Wuhan Jiayuan Quantum Dots Co., Ltd., Wuhan, China) and was the same as indicated in our previous study [45] with the following major steps: deparaffinizing→antigen retrieval→blocking→primary antibodies for Cav-1 and LC3B→washing→biotinylated goat anti-rabbit IgG (for Cav-1)→washing and blocking→605-QD-SA washing and QDs (545 nm) conjugated to goat anti-murine IgG (1:100, Wuhan Jiayuan Quantum Dots Co., Ltd, Wuhan China)→washing→mounting and observation. The QD fluorescent signal was analyzed using the Caliper multispectral microscopy imaging system (Caliper Life Sciences, Hopkinton, MA, USA).…”

Caveolin‐1, cancer and therapy resistance

“…– CAV1 expression in tumor cells may contribute to cell proliferation and was associated with positive HPV‐infection…”

The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

“…At present, the role of Cav-1 in the stromal microenvironment remains unknown. 18 Therefore, further studies are needed to discover the functions of stromal Cav-1 in cervical SCC.…”

“… 12 These evidences indicate that Cav-1 may regard as a tumor suppressor. In contrast, the expression of Cav-1 was reported to increase in prostate cancer, 13 bladder cancer, 14 renal cancer 15 and esophageal SCC, 4 , 16 head and neck SCC (HNSCC), 17 cervical SCC 18 and tongue SCC. 19 Interestingly, these upregulations have also been associated with advanced tumor stage, lymph node metastasis and poor prognosis of cancer patients, which may imply that Cav-1 can function as a tumor promoter.…”