Growth dependency of human colon cancer xenograft on organ environment is related with their original clinical stage.
The ability of cancer cells to metastasize might depend on their reduced dependency on the originating tissue. To test this hypothesis, 10 human colorectal carcinomas (CRC) were implanted either onto nude mouse caecum wall (orthotopic site), or into the subcutaneous tissue (ectopic site), and their growth in these sites compared. Prognostic factors were studied: Astler-Coller modified Dukes's stage, loss of chromosome 17p and/or 18q, and their TP53 gene. Early stage CRC [B2 (n = 3) and C1 (n = 1)] were found to grow 1.7 to 3.6 times (p < 0.05, p < 0.008 respectively) more rapidly in the caecum than in subcutaneous tissue. Metastatic stage CRC [C1 (n = 1), C2 (n = 2) or D (n = 3)] grew similarly in both sites, and more slowly than those of the first group. No relationship was found between growth rates, TP53 mutations or karyotypes. Growth rate of non metastatic cancers was slowed down by implantation in a foreign tissue whereas growth of metastatic tumours was similar in both sites, indicating that they do not recognize or need tissue growth factors.
Pocard
M
M
Section de Recherche, Institut Curie, Paris, France.
Muleris
M
M
Hamelin
R
R
Salmon
R J
RJ
Dutrillaux
B
B
Poupon
M F
MF
D000818:Animals; D002432:Cecum; D002455:Cell Division; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D014183:Transplantation, Heterologous / Q000473:pathology; D014407:Tumor Cells, Cultured