The general research focus of Dr. Colella's laboratory is on proteinases and their inhibitors, especially the lysosomal cysteine proteinases, cathepsins B and L and their endogenous inhibitors, the cystatins. Increased cathepsin activity and/or decreased regulation by their endogenous inhibitors correlate with increased invasive ability of a number of metastatic, cancer cell lines. Furthermore, metastatic cells secrete these lysosomal enzymes leading to the hypothesis that these enzymes are essential for metastasis of cancer cells to distal organs. Our current interests are to examine the role and regulation of cathepsins B and L and their endogenous inhibitors in cancer progression and metastasis. We are studying the effects of the cancer microenvironment on the expression and location of cathepsins B and L and the cystatins. Signaling by cell-cell and cell-matrix interactions have been shown to alter the expression and localization of a number of metastasis associated proteinases including the cathepsins.
Qiu, M., Liu, Z., Li, H., Hu, X., Yu, L., Liu, H., Han, R., Colella, R., Mower, G., and Chen, Y.: Control of precerebellar neuron development by Olig3 bHLH transcription factor. J Neurosci. 28:10124-10133, 2008.
Gopal, P., Rehman, R.U., Chadha, K.S., Mengshing Qiu, and Colella, R.: The influence of Matrigel on the distribution of cathepsin B in prostate cancer PC3 cells. Oncol Rep.16(2):313-20, 2006.
Colella, R., Jackson, T., and Goodwyn, E. (2004). Matrigel® invasion by the prostate cancer cell lines, PC3 and DU145, and cathepsin L+B activity. Biotechnics Histochem. 79:121-127.
Colella, R. & Gopal, P. (2003). Distribution of cathepsins L+B in the prostate cancer cell line, PC3, is dependent on cell culture surface. Am. Assoc. Cancer Res. Proc. 44:767.
Sun, X., Colella, R., & Zacharias, W. (2003). Hypoxia, lysosomal cathepsins, and invasiveness of lung carcinoma cells. Am. Assoc. Cancer Res. Proc. 44:1002.
Colella, R. and Casey, S.F. (2003). Decreased activity of cathepsins L+B with decreased invasive ability of PC3 prostate cancer cells. Biotech. Histochem. 78:101-108.
Colella, R., Goodwyn, E., and Gopal, P. (2002). Increased cell density decreases cysteine proteinase inhibitor activity and increases invasive ability of two prostate tumor cell lines. Cancer Letters 185:163-172.
Colella, R. (1996). Cystatin mRNA is expressed by the ciliary epithelium of the chick eye. J. Histochem. Cytochem, 44: 77-79.
Colella, R., Chambers, A., and Denhardt, D.T. (1993). Anticarcinogenic activities of naturally occurring cysteine proteinase inhibitors. In: Proteinase Inhibitors as Cancer Chemopreventive Agents. Edited by W. Troll and A.R. Kennedy (Plenum Publishing Co.), pp.199-216.
Colella R., Bird J.W.C. (1993). Isolation and characterization of the chicken cystatin gene: Multiple transcription initiation and polyadenylation sites of the cystatin mRNA. Gene, 130: 175-181.
Chambers, A.F., Colella, R., Denhardt, D.T., and Wilson, S.M. (1992). Increased expression of cathepsins L & B, and decreased activity of their inhibitors, in metastatic, ras-transformed NIH 3T3 cells. Molecular Carcinogen. 5:238-245.