Divergent Expression of Caveolin1 in Human Cancer The Case of Lung Cancer

Smoke Free In One Hour

The Painless Stop Smoking Cure

Get Instant Access

The expression of caveolin-1 in different cancer cell lines and tumor samples was documented in numerous studies, and the picture that emerges from these studies is that caveolin-1 expression is highly divergent [6]. Whereas in many cases caveolin-1 expression is down-regulated, in other cancer cells elevated caveolin-1 levels are maintained. High expression of caveolin-1 in cancer cells was initially demonstrated in human multidrug resistant (MDR) cancer cells [43-45] and in mouse metastatic prostate cancer cells [46]. Evidence that has accumulated since these early studies seems to indicate that the expression of caveolin-1 often depends on the tumor's stage and grade. In fact, in most cases where this relationship was examined explicitly, a positive correlation was found between a high expression of caveolin-1 and advanced tumor cell grade and/or progression stage. Such was the case in cancers from the breast [46], prostate [46,47], lung [48,49], bladder [50], kidney [51,52] and pancreas [53,54]. Furthermore, in some cases, high expression of caveolin-1 was shown to be an independent predictor of poor disease prognosis [47,49,51-53,55-58].

The divergent pattern of caveolin-1 in human cancer is well represented in studies of lung cancer tumors and cell lines. Human lung adenocarcinoma- and small cell carcinoma-derived cell lines exhibited little or no caveolin-1 expression, in contrast to high levels of caveolin-1 expression observed in CaLu-1 lung squamous carcinoma cells [59]. However, when compared with normal human lung epithelia, four other lung squamous cell carcinoma lines expressed reduced levels of cav-eolin-1 [60]. In another study, low-level caveolin-1 expression was similarly found in cell lines derived from two lung adenocarcinomas, a bronchioalveolar carcinoma and a large-cell lung carcinoma, whereas non-small-cell lung carcinoma cell lines (Hop-62, Hop-92) highly expressed caveolin-1 [61]. More recently, it was found that about 95 % of small-cell lung cancer (SCLC) cell lines exhibit low or no caveolin-1 expression, whereas a majority (76%) of non-SCLC lines retained high caveolin-1 expression [62].

The loss of caveolin-1 expression in SCLC and in primary non-SCLC was verified immunohistochemically in tumor samples [63,64]. Caveolin-1 expression was reported to be positively correlated with metastatic potential in a series of lung adenocarcinoma cell lines established by selection for increasing invasiveness [48]. The same study found that primary lung adenocarcinoma tumors are largely cav-eolin-1-negative, but there was a significant trend of increased caveolin-1 expression in metastatic lung tumors and in their lymph nodes metastases [48]. Caveolin-1 was prominently down-regulated in primary lung adenocarcinomas, as revealed by DNA microarray analysis [65,66].

Nevertheless, ~25% of lung adenocarcinomas still expressed high levels of caveolin-1 protein, although this study found no correlation of caveolin-1 expression with tumor stage or lymph node status [63]. Other analyses of primary lung squamous cell carcinoma specimens revealed that 26-30% were caveolin-1-posi-tive [49,67]. In these studies there was a significant correlation between caveolin-1 expression and advanced pathologic stage [49,67].

Furthermore, there was a statistically significant decrease in five-year survival after complete resection of patients with caveolin-1-positive tumors [49]. Together, the above data are consistent with a suppression of caveolin-1 gene expression in primary lung tumors (in particular, SCLC). However, some lung tumors and lung cancer cell lines are caveolin-1-positive (notably non-small cell lung carcinoma), and there seems to be a positive correlation between caveolin-1 expression and advanced cancer pathologic stage or metastatic potential. Thus, the status of caveolin-1 in lung cancer is as complex as it is in other forms of cancer.

Was this article helpful?

0 0
Smoking Solutions

Smoking Solutions

How To Maintain The Stop Smoking Pledge From Your New Year’s Resolution. Get All The Support And Guidance You Need To Be A Success At Quitting Smoking. This Book Is One Of The Most Valuable Resources In The World When It Comes To How To Maintain The Stop Smoking Pledge From Your New Year’s Resolution.

Get My Free Ebook


Post a comment