PMID- 11830529
OWN - NLM
STAT- MEDLINE
DCOM- 20020305
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 62
IP  - 3
DP  - 2002 Feb 1
TI  - Interleukin-12 inhibits angiogenesis and growth of transplanted but not in situ 
      mouse mammary tumor virus-induced mammary carcinomas.
PG  - 747-55
AB  - We examined the ability of recombinant murine interleukin-12 (rmIL-12) to inhibit 
      the vasculature and growth of mammary carcinomas arising in situ in mouse mammary 
      tumor virus (MMTV)-infected female C3H/HeN mice. Although it is a potent 
      antiangiogenic and antitumor agent in many transplanted murine tumor models, 
      rmIL-12 failed to inhibit the vascularity, reduce the perfusion, or alter the 
      growth of these autochthonous carcinomas. Factors intrinsic to these tumor cells 
      were unlikely to be responsible for therapy failure. This is because primary 
      cells derived from these carcinomas responded to IFN-gamma, and rmIL-12 was 
      effective against transplanted tumors arising from Mm5MT cells, a line 
      established from a MMTV-induced mammary carcinoma in C3H mice. Factors intrinsic 
      to the mice that host the autochthonous mammary carcinomas were also not 
      responsible for failure, because they sponsored rmIL-12 antiangiogenic and 
      antitumor effects against transplanted K1735 murine melanoma tumors. Instead, the 
      autochthonous nature of the mammary carcinomas and their possession of a high 
      percentage of mature, pericyte-covered vessels that are resistant to therapeutic 
      regression may be responsible. This is supported by the observation that 
      transplanted Mm5MT tumors had a lower proportion of pericyte-covered vessels and 
      responded to rmIL-12 therapy. These results point to significant differences 
      between the vasculature of transplanted and autochthonous murine tumors and 
      indicate that their susceptibility to antivascular therapy may differ 
      substantially.
FAU - Lee, James C
AU  - Lee JC
AD  - Department of Medicine, School of Medicine, University of Pennsylvania, 
      Philadelphia, PA 19104, USA.
FAU - Kim, David C
AU  - Kim DC
FAU - Gee, Michael S
AU  - Gee MS
FAU - Saunders, H Mark
AU  - Saunders HM
FAU - Sehgal, Chandra M
AU  - Sehgal CM
FAU - Feldman, Michael D
AU  - Feldman MD
FAU - Ross, Susan R
AU  - Ross SR
FAU - Lee, William M F
AU  - Lee WM
LA  - eng
GR  - CA 83042/CA/NCI NIH HHS/United States
GR  - P30 CA 16520/CA/NCI NIH HHS/United States
GR  - P30 DK 50306/DK/NIDDK NIH HHS/United States
GR  - R01 CA 45954/CA/NCI NIH HHS/United States
GR  - R01 CA 77851/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Recombinant Proteins)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Cell Division/drug effects
MH  - Disease Models, Animal
MH  - Female
MH  - Interleukin-12/*pharmacology
MH  - Mammary Neoplasms, Experimental/blood supply/*drug therapy/pathology/*virology
MH  - *Mammary Tumor Virus, Mouse
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Neoplasm Transplantation
MH  - Neovascularization, Pathologic/*prevention & control
MH  - Recombinant Proteins/pharmacology
EDAT- 2002/02/07 10:00
MHDA- 2002/03/07 10:01
CRDT- 2002/02/07 10:00
PHST- 2002/02/07 10:00 [pubmed]
PHST- 2002/03/07 10:01 [medline]
PHST- 2002/02/07 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2002 Feb 1;62(3):747-55.