PMID- 7576110
OWN - NLM
STAT- MEDLINE
DCOM- 19951228
LR  - 20191023
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 14
IP  - 3
DP  - 1995 Nov
TI  - The effect of the JE (MCP-1) gene, which encodes monocyte chemoattractant 
      protein-1, on the growth of HeLa cells and derived somatic-cell hybrids in nude 
      mice.
PG  - 179-89
AB  - To investigate the effect of tumor-associated macrophages on the in vivo growth 
      properties of cervical carcinoma cells, tumorigenic human papilloma virus (HPV) 
      18-positive HeLa cells were transfected with an expression vector harboring the 
      cDNA for the macrophage chemoattractant protein-1 JE (MCP-1). Although the 
      endogenous gene is present and not structurally rearranged, its expression seems 
      to be negatively affected by a still unknown mechanism. Inoculation of JE 
      (MCP-1)-negative HeLa cells into nude mice led to rapidly growing tumors, where 
      macrophage infiltration into the inner tumor mass was not detectable 
      immunohistochemically. The activity that attracted mononuclear cells under both 
      in vitro and in vivo condition was reconstituted in HeLa cells after transfection 
      with the JE (MCP-1) expression vector. Heterotransplantation of those cells into 
      immunocompromised animals resulted in significant growth retardation that was 
      accompanied by a strong infiltration of macrophages. On the other hand, in vivo 
      selection of nonmalignant hybrids made between wild-type HeLa cells and normal 
      human fibroblasts in nude mice resulted in tumorigenic segregants 4 mo after 
      inoculation into the animals. Monitoring JE (MCP-1) expression directly within 
      those nodules, we found that transcription was either absent or only weakly 
      detectable. Recultivation of JE (MCP-1)-positive tissue grafts under in vitro 
      conditions revealed that the gene was only marginally inducible by tumor necrosis 
      factor-alpha, a cytokine that normally induces a very strong activation of 
      transcription in nontumorigenic cells. These findings suggest that functional JE 
      (MCP-1) expression and in turn activated macrophages may play a pivotal role in 
      controlling the proliferation rate of HPV-positive cells in vivo.
FAU - Kleine, K
AU  - Kleine K
AD  - Deutsches Krebsforschungszentrum, Heidelberg, Germany.
FAU - Konig, G
AU  - Konig G
FAU - Kreuzer, J
AU  - Kreuzer J
FAU - Komitowski, D
AU  - Komitowski D
FAU - Zur Hausen, H
AU  - Zur Hausen H
FAU - Rosl, F
AU  - Rosl F
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cell Division
MH  - Chemokine CCL2/*genetics/physiology
MH  - DNA, Complementary/genetics
MH  - Gene Expression
MH  - Gene Expression Regulation/physiology
MH  - HeLa Cells
MH  - Humans
MH  - Hybrid Cells
MH  - Immunohistochemistry
MH  - Macrophages/physiology
MH  - Mice
MH  - Mice, Nude
MH  - Papillomaviridae
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - Simian virus 40/genetics
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1995/11/01 00:00
MHDA- 1995/11/01 00:01
CRDT- 1995/11/01 00:00
PHST- 1995/11/01 00:00 [pubmed]
PHST- 1995/11/01 00:01 [medline]
PHST- 1995/11/01 00:00 [entrez]
AID - 10.1002/mc.2940140307 [doi]
PST - ppublish
SO  - Mol Carcinog. 1995 Nov;14(3):179-89. doi: 10.1002/mc.2940140307.