Secreted growth factors from estrogen receptor-negative human breast cancer do not support growth of estrogen receptor-positive breast cancer in the nude mouse model.
Estrogen receptor (ER)-negative MDA-231 human breast cancer cells have been shown to secrete high concentrations of several growth factors including transforming growth factor-alpha and insulin-like growth factor I, which could have important autocrine or paracrine growth regulatory functions and, additionally, could explain the rapid autonomous growth of these cells. In contrast, the hormone-responsive, ER-positive MCF-7 cells secrete low levels of these factors constitutively. Since estrogen treatment increases secretion of these growth factors in MCF-7 cells, it has been postulated that these growth factors mediate estrogen's growth effects through an autocrine mechanism. To test this hypothesis we reasoned that growth factors supplied by MDA-231 cells should support growth of MCF-7 cells in an estrogen-depleted environment. Inoculation of castrated female athymic nude mice with MDA-231 cells resulted in rapid tumor growth. However, MDA-231 tumors did not support growth of MCF-7 cells inoculated on the opposite flank by an endocrine mechanism; MCF-7 tumors required estrogen supplementation for growth. To determine if MDA-231 cells could support MCF-7 growth by a paracrine mechanism, various mixtures of the two cell lines were coinoculated at the same site in castrated or in estrogen-supplemented mice. ER was not detectable in tumors derived from a mixed inoculum, indicating the absence of MCF-7 cell growth. Furthermore, DNA flow cytometry of these tumors revealed only a single G1 peak representative of MDA-231 cells in estrogen-deprived mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Osborne
C K
CK
Department of Medicine/Oncology, University of Texas Health Science Center, San Antonio 78284.
Ross
C R
CR
Coronado
E B
EB
Fuqua
S A
SA
Kitten
L J
LJ
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011960:Receptors, Estrogen / Q000032:analysis; D013002:Somatomedins / Q000502:physiology*; D015291:Transforming Growth Factors / Q000235:genetics / Q000502:physiology*; D014183:Transplantation, Heterologous
D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors