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

Authors: YAO, YIWEN - Tongji Medical College; WU, JUNLU - Tongji Medical College; ZHOU, HAO - Tongji Medical College; Firrman, Jenni; XIAO, WEIDONG - Temple University Medical School; SUN, ZUJUN - Tongji Medical College; LI, DONG - Tongji Medical College

Submitted to: American Journal of Cancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/25/2018
Publication Date: 7/15/2018
Citation: Yao, Y., Wu, J., Zhou, H., Firrman, J., Xiao, W., Sun, Z., Li, D. 2018. A deficiency in cathelicidin reduces lung tumor growth in NNK/NTHi-induced A/J mice. American Journal of Cancer Research. 8(7):1190-1199.

Interpretive Summary: Human cells make and release an antimicrobial compound called cathelicidin, which protects the human cells from harmful bacteria but may also be involved in tumor growth. In order to study whether or not cathelicidin plays a role in tumor formation, a unique mouse model was generated in which the mice were not able to make cathelicidin. Compared to normal mice, the mice that cannot make cathelicidin had less tumors and longer survival time, when challenged with lung cancer. This provides evidence that that cathelicidin may be involved with lung cancer development. Based on these results, this unique mouse model can be used to further study cathelicidin and its role in tumor growth and formation.

Technical Abstract: 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.