Caveolin-1, CAV-1

Caveolin-1 is a 22 kDa membrane protein which is expressed by mesenchymal cells.  It is a structural component of caveolae, 80 to 100 nm omega-shaped vesicular invaginations of the plasma membrane2,3.  It has putative functions in vesicular transport, cholesterol homeostasis, cell migration, cell cycle and cell polarity regulation.  It is commonly up-regulated in malignant neoplasms.  Cav1 has been variously reported to impact both positively and negatively on various aspects of tumour progression, being both reported to function as a tumour suppressor and identified as a poor prognostic factor in various human cancers4,5.  It reportedly expression correlates with drug resistance and a poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy10.  However, it is also said to be down-regulated in human lung carcinoma, acting as a candidate tumour suppressor gene11.  Caveolin-1  is also thought to play an important roles in organogenesis6 and atherosclerosis7.

Immunohistochemical expression

• Endothelial cells
• Smooth muscle cells
• Type I and II pneumocytes:  type I pneumocytes have caveolae, some of which show immunogold localisation of caveolin.  Type II pneumocytes label for caveolin but lack caveolae8.
• Mesothelial cells9

In lung carcinomas, staining is predominantly membrane with cytoplasmic staining in a minority of cases12.  There is variation in the rate of expression with subtype.  Primary tumours showing metastatic spread are more often positive for caveolin-1.  Brain but not adrenal metastases may acquire positivity where the primary lung tumour was negative12.

Diagnostic utility

Differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma:

References

1 Amatya, V. J., Y. Takeshima, et al. (2009). "Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma." Histopathology 55(1): 10-19.

2 Glenney, J. R., Jr. and D. Soppet (1992). "Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts." Proc Natl Acad Sci U S A 89(21): 10517-10521.

3 Rothberg, K. G., J. E. Heuser, et al. (1992). "Caveolin, a protein component of caveolae membrane coats." Cell 68(4): 673-682.

4 Goetz, J. G., P. Lajoie, et al. (2008). Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metastasis Rev 27(4): 715-735.

5 Quest, A. F., J. L. Gutierrez-Pajares, et al. (2008). "Caveolin-1: an ambiguous partner in cell signalling and cancer." J Cell Mol Med 12(4): 1130-1150.

6 Fang, P. K., K. R. Solomon, et al. (2006). Caveolin-1alpha and -1beta perform nonredundant roles in early vertebrate development. Am J Pathol 169(6): 2209-2222.

7 Frank, P. G., S. E. Woodman, et al. (2003). Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol 23(7): 1161-1168.

8 Newman, G. R., L. Campbell, et al. (1999). "Caveolin and its cellular and subcellular immunolocalisation in lung alveolar epithelium: implications for alveolar epithelial type I cell function." Cell Tissue Res 295(1): 111-120.

9 von Ruhland CJ, Campbell L, Gumbleton M, Jasani B, Newman GR. Immunolocalization of caveolin-1 in rat and human mesothelium. J Histochem Cytochem. 2004 Nov;52(11):1415-25.

10 Ho CC, Kuo SH, Huang PH, Huang HY, Yang CH, Yang PC. Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy. Lung Cancer. 2008 Jan;59(1):105-10.

11 Belanger MM, Roussel E, Couet J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene. Chest. 2004 May;125(5 Suppl):106S.

12 Cassoni P, Daniele L, Maldi E, Righi L, Tavaglione V, Novello S, et al. Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases. Histopathology. 2009 Jul;55(1):20-7.

This page last revised 15.8.2009.

©SMUHT/PW Bishop