Establishment and characterization of a murine xenograft model of appendiceal mucinous adenocarcinoma.
We describe the clinical, pathologic and molecular characteristics of a xenograft model of metastatic mucinous appendiceal adenocarcinoma. Tumours from patients with mucinous appendiceal neoplasms were implanted in nude mice and observed for evidence of intraperitoneal tumour growth. Morphologic and immunohistochemical features, temporal growth characteristics relative to controls, and loss of heterozygosity (LOH) at multiple chromosomal alleles were assessed in a successfully engrafted tumour. Two of seventeen implanted tumours successfully engrafted and only one mucinous adenocarcinoma propagated throughout the course of the study. The successful xenograft is morphologically similar to the original tumour, produces abundant extracellular mucin and exhibits non-invasive growth on peritoneal surfaces. The temporal growth characteristics of the xenograft tumour relative to controls reveal that tumour burden can be followed indirectly by measuring the weight or abdominal girth of engrafted animals. The cytokeratin, mucin core protein, CDX2, Ki-67 and p53 expression patterns are identical in the xenograft and resected tumour and are consistent with the expected pattern of protein expression for mucinous adenocarcinoma of the appendix. LOH was found in 1 of 10 informative chromosomal loci (chromosome 10p23) in xenograft tumour cells. Although we were unable to engraft a low-grade appendiceal mucinous neoplasm, the engrafted adenocarcinoma will be useful for future evaluation of novel therapeutic strategies directed at mucinous appendiceal adenocarcinoma and evaluation of strategies for treating widespread, bulky, mucinous peritoneal surface neoplasms. Xenograft tumour enrichment can facilitate molecular studies of appendiceal epithelial neoplasia.
Mavanur
Arun A
AA
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Parimi
Vamsi
V
O'Malley
Mark
M
Nikiforova
Marina
M
Bartlett
David L
DL
Davison
Jon M
JM
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D001063:Appendiceal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071616:CDX2 Transcription Factor; D049109:Cell Proliferation; D002879:Chromosomes, Human, Pair 10; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D019656:Loss of Heterozygosity; D051379:Mice; D008819:Mice, Nude; D009077:Mucins / Q000378:metabolism; D009154:Mutation; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013997:Time Factors; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000235:genetics
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C117307:KRAS protein, human; D019394:Ki-67 Antigen; D009077:Mucins; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007633:Keratins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins