Mechanisms mediating the effects of IL-3 gene expression on tumor growth.
IL-3 gene expression within tumors leads to host-cell infiltration, particularly by macrophages, slower tumor growth, and enhanced immunogenicity. Surprisingly, tumor-associated macrophages (TAMs) from within FSAN-JmIL3 tumors had decreased expression of TNF-alpha and iNOS. On short-term culture, TAMs from FSAN-JmIL3 tumors regained their capacity to produce TNF-alpha and NO, indicating that they were primed in vivo. In vitro experiments were unable to demonstrate differences between FSAN-JmIL3 and FSAN tumor cells in their ability to stimulate TNF-alpha production by TAMs. In the absence of evidence that TAM activation was responsible for the slower growth of FSAN-JmIL3 tumors, the response of tumor cells to these effector molecules was studied. TNF-alpha and NO were cytotoxic for FSAN-JmIL3 cells but growth stimulatory for FSAN. These tumor-related phenotypic changes may contribute as much if not more than functional changes in host infiltrating cells to the slower growth of FSAN-JmIL3 tumors in vivo.
Wu
Y Z
YZ
Department of Atomic Science, Tsing Hua University, Hsinchu, Taiwan.
Hong
J H
JH
Huang
H H
HH
Dougherty
G J
GJ
McBride
W H
WH
Chiang
C S
CS
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D015972:Gene Expression Regulation, Neoplastic; D007377:Interleukin-3 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008175:Lung Neoplasms / Q000556:secondary; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D018076:DNA, Complementary; D007377:Interleukin-3; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse