Wnt/β-catenin expression does not correlate with serum alkaline phosphatase concentration in canine osteosarcoma patients.
Osteosarcoma is an aggressive malignancy of the bone and an increase in serum alkaline phosphatase concentration has clinical prognostic value in both humans and canines. Increased serum alkaline phosphatase concentration at the time of diagnosis has been associated with poorer outcomes for osteosarcoma patients. The biology underlying this negative prognostic factor is poorly understood. Given that activation of the Wnt signaling pathway has been associated with alkaline phosphatase expression in osteoblasts, we hypothesized that the Wnt/β-catenin signaling pathway would be differentially activated in osteosarcoma tissue based on serum ALP status. Archived canine osteosarcoma samples and primary canine osteosarcoma cell lines were used to evaluate the status of Wnt/β-catenin signaling pathway activity through immunohistochemical staining, western immunoblot analyses, quantitative reverse-transcription polymerase chain reaction, and a Wnt-responsive promoter activity assay. We found no significant difference in β-catenin expression or activation between OSA populations differing in serum ALP concentration. Pathway activity was mildly increased in the primary OSA cell line generated from a patient with increased serum ALP compared to the normal serum ALP OSA cell line. Further investigation into the mechanisms underlying differences in serum ALP concentration is necessary to improve our understanding of the biological implications of this negative prognostic indicator.
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Caroline M
CM
Piskun
Anantharaman
A
Muthuswamy
Michael K
MK
Huelsmeyer
Victoria
V
Thompson
Timothy J
TJ
Stein
D000469:Alkaline Phosphatase / Q000097:blood*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004283:Dog Diseases / Q000097:blood* / Q000201:enzymology* / Q000235:genetics; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D012516:Osteosarcoma / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D021381:Protein Transport; D014020:Tissue Extracts; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D014020:Tissue Extracts; D051176:beta Catenin; D008156:Luciferases; D000469:Alkaline Phosphatase