Differential expression of transforming growth factor beta 1 and interleukin 10 in progressing and regressing areas of primary melanoma.
The coexistence of tumor specific immunity with a progressing tumor remains a major paradox of tumor immunology. This enigma is most evident in partially regressing melanomas, where efficient eradication of tumor cells is closely linked to uncontrolled tumor growth. Mechanisms involved in this differential susceptibility of tumor cells to the host immune response may include altered production of immunosuppressive cytokines, i.e., transforming growth factor (TGF) beta or interleukin (IL) 10. Since only limited amounts of tissue samples are available from primary tumors, a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was established which allowed to estimate the amount of cytokine mRNA expressed in a small number of melanoma cells segregated by indirect immunomagnetic isolation. Thereby, we determined the expression of TGF-beta 1 and IL-10 mRNA in melanoma cells obtained from regressing and progressing areas of 9 primary tumors. TGF-beta 1 mRNA could be detected in all undiluted samples from progressing areas and in 7 samples from regression zones. Titration of the sample revealed that in 6 cases TGF-beta 1 mRNA could be detected at a significant higher titer in progressing than in regressing areas. IL-10 mRNA was present in 8 samples obtained from progressing and in 7 samples from regressing tumor areas. In 6 tumors IL-10 mRNA was detectable at a higher titer in the progression zones. Specificity of the PCR amplification was confirmed with a series of restriction enzyme digestions of the resulting PCR product. Based on these findings the hypothesis that immunosuppressive cytokines, such as TGF-beta 1 or IL-10, represent important factors for the melanoma cells to escape immune surveillance is supported.
Conrad
C T
CT
Department of Dermatology, University of Würzburg, FRG.
Ernst
N R
NR
Dummer
W
W
Bröcker
E B
EB
Becker
J C
JC
D018450:Disease Progression; D006801:Humans; D007108:Immune Tolerance; D007157:Immunologic Surveillance; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008545:Melanoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D009365:Neoplasm Regression, Spontaneous; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10