Exogenous α-defensin increases motility of prostate, follicular thyroid and pancreatic cancer cell lines.

Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B72 Exogenous α-defensin increases motility of prostate, follicular thyroid and pancreatic cancer cell lines. Introduction: α-Defensin (α-DEF) is a cytotoxic peptide with a recognized role in pathogen killing and the innate immune system. We have previously published that α-DEF, also known as human neutrophil protein-1, is more highly expressed in invasive than non-invasive transitional cell carcinoma of bladder (TCC) in vivo and that exogenous peptide significantly increased the proliferation, motility and invasiveness of TCC in vitro . The current studies were designed to determine whether α-DEF increases the motility of other cancer types including prostate cancer, follicular thyroid cancer and pancreatic cancer. Methods: Doses of α-DEF ranging from 0.8μg/ml to 25μg/ml were analyzed for cell motility changes Boyden chamber motility assays. The cell lines examined included the prostate cancer cell line DU-145, the pancreatic cell line Pan-C1 and two follicular thyroid cell lines from the same patient. The first was FTC-133 derived from the primary tumor and the second was FTC-238 derived from a lung metastasis. Results: These studies demonstrated that exogenous α-DEF increased cancer cell motility for all the cell types studied as demonstrated for TCC. There were several unexpected results however. For all the TCC lines previously studied the optimum dose for motility was 12.5μg/ml reaching a maximum motility index (MMI) of only 1.4. Every cell type examined in these studies was more responsive to α-defensin than the TCC cells. The MMI for FTC-133 was 2.7 at the 3.1μg/ml dose and 5.37 for FTC-238 at the same dose. Pan-C1 cells were the also responsive to the peptide with the MMI of 4.64 at 6.3 μg/ml. DU-145 cells were evaluated at doses from 3.1-25μg/ml and these cells reached their MMI of 3.48 at the lowest dose tested. Conclusions: These studies demonstrate that α-DEF is able to dramatically increase the motility of every cancer type studied at lower doses and with greater increases than demonstrated for TCC. These results indicate that α-DEF may be an important molecule for progression of several cancers linking inflammation and cancer progression in a previously unappreciated way extending the work of the previous TCC studies. Future studies will evaluate changes in cell invasion with this peptide and investigate the mechanism(s) by which this peptide exerts its influence upon cancer.