Varying patterns of expression of insulin-like growth factors I and II and their receptors in murine mammary adenocarcinomas of different metastasizing ability.
We studied the expression of insulin-like growth factors I (IGF-I) and II (IGF-II) and their receptors (IGF-R) in 2 related murine mammary adenocarcinoma in vivo lines, M3 and MM3, with different metastasizing ability. We further investigated the effects of IGFs on the secretion of a key enzyme in the metastatic cascade, the urokinase-type plasminogen activator (uPA) in M3 and MM3 cells. M3 is a spontaneous mammary tumor originated in BALB/c mice, with a 40% incidence of lung metastases. MM3 variant, obtained by successive s.c. implants of M3 lung metastases into syngeneic mice, shows a 95% incidence of lung metastases. Similar levels of expression of IGF-I protein were found in M3 and MM3 tumors, whereas IGF-II expression was 4-fold higher im MM3. RNAse protection assays showed similar levels of IGF-I mRNA in M3 and MM3 tumors and revealed a 4-fold increase in IGF-II transcripts in MM3 tumors compared with M3. Authentic IGF-I and II messages were also found in primary cultures of M3 and MM3 cells. IGF-I mRNA levels were similar in both cultures and, as described for solid tumors a 5-fold increase in IGF-II message was detected in MM3 cells. The presence of type I and mannose-6-phosphate (Man-6P)/type II IGF-R was demonstrated in both M3 and MM3 tumors. A 2-fold increase of type I IGF-R was detected in MM3 tumors compared with M3. Man-6P/type II IGF-R levels were 2-fold lower in MM3 tumors than in M3. As observed in tumor membranes, type I IGF-R concentrations were higher and Man-6P/type II IGF-R lower in cultures of MM3 epithelial cells compared with MM3 cells. In addition, we found that IGF-I enhanced secreted uPA activity in both M3 and MM3 cells while IGF-II only stimulated uPA secretion in MM3 cells.
Guerra
F K
FK
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Eijan
A M
AM
Puricelli
L
L
Alonso
D F
DF
Bal de Kier Joffé
E
E
Kornblihgtt
A R
AR
Charreau
E H
EH
Elizalde
P V
PV
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D014568:Urokinase-Type Plasminogen Activator