Abstract
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.
Highlights
Osteosarcoma (OSA) is the most common primary bone malignancy of humans [1]
There was no difference in the relative expression of b-catenin mRNA in tumor samples from dogs with increased serum alkaline phosphatase (ALP) concentration compared to tumor samples from dogs with normal serum ALP concentration (Figure 1A)
Serum alkaline phosphatase (ALP) concentration has been correlated with overall survival times and disease-free intervals, and an increased serum ALP concentration is a negative prognostic indicator for both human and canine OSA patients [9,10,11,12]
Summary
Osteosarcoma (OSA) is the most common primary bone malignancy of humans [1]. A notably aggressive disease, relapse and/or metastasis occurs in 80% of cases [2]. Similar to the human disease, osteosarcoma accounts for 85–98% of all canine bone tumors [6,7]; and pulmonary metastasis occurs in 90% of cases following removal of the primary tumor [7,8]. A better understanding of osteosarcoma is necessary, as despite advances in treatment regimens, the median survival time for either humans or dogs with osteosarcoma has not changed drastically in the last 10–20 years [1,2,3,9] In both species, prognosis worsens with increased serum alkaline phosphatase (ALP) concentration, correlating with shorter survival and disease-free intervals [10,11,12,13]
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