The mouse parathyroid hormone-like hormone Pthlh(Pro) and Pthlh(Thr) variants 
are linked with susceptibility and resistance to skin carcinogenesis of Car-S 
and Car-R mice, respectively, and with in vitro effects (Oncogene, 19: 
5324-5328, 2000). We have identified an additional Pthlh variant, consisting of 
Thr and three amino-acid changes in the C-terminus (Pthlh(SerAspTyr)), carried 
by an evolutionarily distant Mus spretus (SPRET/Ei) inbred strain. When 
transfected into NCI-H520 tumor cells, this Pthlh(SerAspTyr) variant did not 
stimulate tumor growth in nude mice. Analysis of cell adhesion, migration, and 
invasion patterns of Pthlh(Pro)-, Pthlh(Thr)-, and Pthlh(SerAspTyr)-transfected 
NCI-H520 cells revealed a 1.5-fold decrease in adhesion efficiency on both 
collagen type I and Matrigel, and a 5-6-fold increase in migration capability in 
Pthlh(Pro) transfectants as compared to nontransfected, vector-transfected, 
Pthlh(Thr)-, or Pthlh(SerAspTyr)-transfected cells. These findings suggest that 
the cancer modifier effects of the mouse Pthlh gene are mediated by differential 
cell adhesion and migration effects of PTHrP variants.