The microscopic anatomy of experimental rat CC531 colon tumour metastases: consequences for immunotherapy?
The colon adenocarcinoma cell line CC531 was adopted as a model for immunotherapeutical treatment of experimental colorectal metastases in a syngeneic rat model. We studied the presence and localization of T and natural killer cells, vessels and matrix proteins in in vivo growing CC531 tumours by immunohistochemistry. CC531 tumours were induced either in the lungs by injecting CC531 tumour cells into a tail vein or in the liver by injection of CC531 tumour cells under the liver capsule or into a mesenteric vein. All 3 tumour types were composed of islets of tightly apposed tumour cells surrounded by abundantly present tumour-stroma which contained tumour vessels and matrix proteins. Some of these matrix proteins, especially laminin and collagen IV formed a basal membrane-like structure around the tumour nodules. This structure was most pronounced in mesenteric vein-induced liver tumours and less prominent in subcapsular-induced liver tumours and tail vein-induced lung tumours. Tumour-infiltrating lymphocytes of both T and natural killer cell origin were found in the tumours, but predominantly in the tumour stroma, separated from the islets of tumour cells by the basal membrane-like structure. We hypothesize that the matrix proteins of these tumours play an ambivalent role: they may provide a substratum for migration of effector cells into the tumour stroma but may also provide a barrier preventing direct contact between tumour target cells and immune effector cells.
Hagenaars
M
M
Department of Surgery, Leiden University Medical Center, The Netherlands.
Ensink
N G
NG
Basse
P H
PH
Hokland
M
M
Nannmark
U
U
Eggermont
A M
AM
van de Velde
C J
CJ
Fleuren
G J
GJ
Kuppen
P J
PJ
D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000166:cytology; D008297:Male; D009362:Neoplasm Metastasis; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology