New perspectives in hormone-dependent (responsive) and autonomous mammary tumor growth: role of autostimulatory growth factors.

In this report, we present evidence that estrogen-dependent rat mammary tumor cells produce autostimulatory (autocrine) growth factors in response to estrogens, and that hormone autonomous cells produce autocrine activities that are no longer under estrogen regulation. Confirmation of the in vivo significance of autostimulatory factors was sought by inoculating rats with mixed populations of estrogen-dependent, responsive, and autonomous MTW9/PL mammary tumor cells, and showing that after 16 weeks growth in castrated male rats, the estrogen-dependent and responsive mammary tumor cells not only survived, but continued to grow. Three out of seven of the clones derived from apparently autonomous tumors were shown to be estrogen-dependent or responsive. These are the first data establishing that estrogen-dependent (responsive) mammary tumor cells are able to grow in the absence of physiological concentrations of sex steroid hormones in vivo, and that autocrine factors secreted from adjacent autonomous cells are able to substitute for the steroid hormone requirement.