Abstract
Cancer cells have an obligate need for cobalamin (vitamin B12) to enable DNA synthesis necessary for cellular replication. This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues. All malignant tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species. There was a strong correlation between TCII and TCII-R expression, and a modest correlation between TCII-R and Ki-67 expression in both species; a modest association between TCII and Ki-67 expression was present in canine tissues only. These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors. The potential to utilize these proteins as biomarkers to identify neoplastic tissues, streamline therapeutic options, evaluate response to anti-tumor therapy and monitor for recurrent disease has important implications in the advancement of cancer management for both human and companion animal patients.
Highlights
As the ‘one treatment fits all’ paradigm disappears from clinical cancer medicine, there is an increasing demand for the discovery and development of new cancer biomarkers to facilitate the transition to individualized patient care
The soft tissue sarcoma tumor group was represented by a thoracic soft tissue sarcoma, a soft tissue sarcoma over the elbow and a peripheral nerve sheath tumor
Since the original isolation and crystallization of cobalamin in 1948 [25, 26], this study is the first to quantify on a molecular level the expression of the cobalamin transport protein and cell surface receptor in canine and feline malignant tumors
Summary
As the ‘one treatment fits all’ paradigm disappears from clinical cancer medicine, there is an increasing demand for the discovery and development of new cancer biomarkers to facilitate the transition to individualized patient care. Biomarkers offer the potential for improved diagnostic and therapeutic efficacy and reduced toxicity compared to traditional tumor management options [1, 2]. The ideal cancer biomarker is one which can be used to diagnose disease at an early stage, tailor therapy specific to each patient, monitor response to therapy, recognize potential therapeutic toxicities, define prognosis and monitor disease progression or recurrence [3,4,5]. The transcobalamin II transport protein (TCII) and cell surface receptor (TCII-R) are essential proteins involved in Cbl transport and uptake, and are expressed in all mammalian species [13]. The TCII-Cbl complex travels to the cell membrane surface and undergoes receptor-mediated endocytosis via TCII-R, which recognizes TCII-bound Cbl [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
