Characterization of the Hormone-Sensitivity of Three Human Non-Small-Cell Lung Cancers Grafted onto Nude Mice

Abstract

The in vivo hormone sensitivity of three human NSCLCs grafted onto female nude mice (labelled KLX7, KLX9 and KLX14) was characterized on a dynamic level, i.e. on the level of both the macroscopic growth and the proliferative fraction (PF = percentage of cells in the S + G2 + M Fractions). Two sets of experiments were performed. The first set showed the influence on the macroscopic growth of the NSCLC xenograft of castration performed either before or after tumor grafting. The second set showed the influence of a pulse of 6 different hormones or growth factors on the PF index magnitude recorded 36 h after their administration to the xenograft-bearing mice. These 6 hormones or growth factors were EGF, estradiol-17-beta (E2). gastrin (G), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and bombesin (B). The results show that the KLX7 model grew definitely faster on the nude mice than the other two models. Ovariectomy before or after tumor grafting did not significantly modify the growth pattern of the KLX7 model, while castration before tumor grafting significantly increased the macroscopic growth of both the KLX9 and the KLX14 tumors. In contrast, E2, bFGF, G and B significantly increased the proliferative activity of the KLX7 model 36 h after their administration to the tumor-bearing mice while remaining without any apparent statistically significant effects in both the KLX9 and the KLX14 models.

Reproductive and hormonal factors and the risk of nonsmall cell lung cancer

“…Estrogen may also aid in the formation of PAH‐related DNA adducts 39. Laboratory studies in rodents support a role of estrogen in the promotion of nonsmall cell lung cancer 40. Although this evidence suggests that greater exposure to endogenous and exogenous estrogen would, if anything, lead to an increased risk of lung cancer, in general, this hypothesis has not been strongly supported by results from epidemiologic studies.…”