Progression from hormone dependence to autonomy and angiogenesis in mouse mammary tumours

Abstract

The transplantable pregnancy-dependent mammary tumour (TPDMT-4), the related hormone-dependent (TPDMT-4EP) and autonomous (T4-0I320 and T4-0I96) subline tumours, and the mammary glands from DDD mice were compared for angiogenic activity on the rabbit cornea by tissue implantation. The TPDMT-4EP tumour was established by serially transplanting TPDMT-4 tumour fragments in oestradiol plus progesterone treated mice. The T4-0I320 and T4-0I96 tumours directly derived from the TPDMT-4 and TPDMT-4EP tumours, respectively. Angiogenic activity was graded by macroscopic and microscopic examinations into 3 classes; negative, partial and complete angiogenesis. These tumours were comparable to mammary glands in activity and induced complete angiogenesis in only 15-23% of the implants. However, when partial and complete responses were combined as positive angiogenesis, TPDMT-4, T4-0I320, TPDMT-4EP and T4-0I96 tumour implants were angiogenic in 25, 29, 42 and 54%, respectively. The T4-0I96 tumour was significantly more angiogenic than the parent tumour but this was not so for the TPDMT-4EP tumour. Spontaneous C3H mouse mammary tumours, human gliomas from nude mice, rat Walker 256 carcinomas and rabbit VX-2 tumours induced complete angiogenesis in 54, 63, 59 and 92% of the implants, respectively. The results suggest that the TPDMT-4 tumour is unique in being weakly angiogenic and able to progress toward greater autonomy with or without augmented angiogenic activity in different conditions.