Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases.
This investigation aimed to develop a biologically relevant murine model of colorectal liver metastases and determine if Kupffer cells (KC) and hepatic natural killer cells (hNKC) regulate tumor growth. The model involves the injection of murine colon adenocarcinoma 26 (MCA 26) tumor cells into the portal vein of female-specific pathogen-free BALB/c mice. Metastases developed in all animals, and the growth was limited entirely to the liver. To determine if KC and hNKC control the development of liver metastases, the in vivo function of these hepatic effector cells was modulated. Tumor growth was quantitated by the uptake of 125I into tumor DNA. Stimulation of the KC and hNKC produced a significant (P less than 0.01) dose-dependent decrease in 125I uptake in the liver in both treatment groups, which was associated with a significant improvement in survival (P less than 0.05). The in vivo cytotoxic function of the liver was inhibited with an intravenous injection of gadolinium chloride (for KC) or asialo GM1 antiserum (for hNKC). Inhibition of KC and hNKC cytotoxic function led to a significant (P less than 0.01) increase in 125I uptake in the liver and a significant decrease in survival (P less than 0.05).
Roh
M S
MS
Section of Natural Immunity, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Kahky
M P
MP
Oyedeji
C
C
Klostergaard
J
J
Wang
L
L
Curley
S A
SA
Lotzová
E
E
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology*; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology / Q000502:physiology; D005682:Gadolinium / Q000494:pharmacology; D007106:Immune Sera; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D011425:Propionibacterium acnes / Q000276:immunology; D012004:Rectal Neoplasms / Q000276:immunology / Q000473:pathology*
D000970:Antineoplastic Agents; D007106:Immune Sera; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D003596:Cytosine; D005682:Gadolinium; C033560:bropirimine; C038958:gadolinium chloride