A deficiency in cathelicidin reduces lung tumor growth in NNK/NTHi-induced A/J mice.

Cathelicidin is an antimicrobial peptide that plays an essential role in cell proliferation, angiogenesis, and also has been indicated in tumor promotion. However, it is unclear how cathelicidin causes tumor growth, and the pathogenic mechanisms based on gain or loss of function have not been proposed. Here, a cathelicidin related antimicrobial peptide (CRAMP) knockout mouse was generated using an A/J background (A/J-CRAMP-/- mice), and lung carcinoma growth was induced using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and Non-typeable Haemophilus influenzae (NTHi). Compared with A/J mice, A/J-CRAMP-/- mice were found to have a lower tumor burden and longer survival times, with a significant reduction in both PCNA and Ki-67 positive cells. However, there was no difference between the number of apoptotic lung-cancer cells between the A/J and A/J-CRAMP-/- mice. This indicated cathelicidin might be a tumor growth factor for lung cancer, which was associated for proliferation of tumor cells. In the future, this animal model will be useful to study the distinct role of cathelicidin in induced-lung cancer development.