Leukaemia Inhibitory Factor derived from rat colon carcinoma cells increases host susceptibility to tumour growth.
We have tested Leukaemia Inhibitory Factor (LIF) production by 12 rat colon tumour clones isolated from a single cell line that display various degrees of tumorigenicity. A highly significantly relationship was found between levels of soluble LIF produced by the clones and their in vivo tumorigenicity. Such results suggested a role for LIF as a tumour facilitating agent. To test this hypothesis, the highly tumorigenic and LIF producing PROb clone was transfected with the LIF cDNA in antisense orientation in order to decrease LIF production. Conversely, REGb, a low LIF producer that is rejected by syngeneic animals, as well as nude mice, was transfected with the LIF cDNA to increase its production. PROb cells transfected with antisense cDNA were shown to have decreased LIF production along with decreased tumorigenicity. LIF-transfected REGb cells expressing high LIF levels still regressed in syngeneic rats, but could form progressive tumours in nude mice. We did not detect LIF receptors on PROb or REGb cells and their in vitro proliferation was not modified by the addition of exogenous LIF. Therefore, LIF was not an autocrine growth regulator for PROb and REGb cells. Instead, LIF appears to facilitate in vivo tumour growth, without being an immunosuppressive factor sufficient on its own to allow growth of immunogenic cells in fully immunocompetent hosts.
Burg
C
C
Institut de Biologie, Nantes, France.
Patry
Y
Y
Le Pendu
J
J
Moreau
M
M
Tesson
L
L
Godard
A
A
Soulillou
J P
JP
Meflah
K
K
Anegon
I
I
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004198:Disease Susceptibility; D005822:Genetic Vectors; D005914:Globins / Q000235:genetics; D006084:Graft Rejection; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6; D007438:Introns; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D015183:Restriction Mapping; D014162:Transfection; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011994:Recombinant Proteins; D005914:Globins