Sheila Figel, PhD, a neuro-oncologic scientist with Roswell Park Comprehensive Cancer Center, discusses preclinical research with canonical and noncanonical that are displayed on the surface of cancer cells.
Sheila Figel, PhD, a neuro-oncologic scientist with Roswell Park Comprehensive Cancer Center, discusses preclinical research with canonical and noncanonical survivin isoforms that are displayed on the surface of cancer cells.
For their research, Figel and colleagues set out to express the different types of transcripts in multiple cell type backgrounds, including an embryonic cell line that was representative of developmental tissue (HAK 293), and several tumor cell lines, which included cervical adenocarcinoma and glioblastoma.
When this was done across different cell lines, investigators found that in addition to the canonical isoform, the Δex3 and 2B isoforms of survivin, which are known to be expressed in different cancer types, were being shuttled to the plasma membrane and were being expressed on the outside of cancer cells. This indicates that since this can be observed in the system, it is possible that this is also happening in real tumors within patients. This theory will be further examined in a follow-up study, Figel adds.
Additional findings were reported from analyses that focused on sequence of the isoforms. The isoforms differ in their C-termini but they share the Baculovirus IAP Repeat domain, which is known to have a role in antiapoptosis or survival, Figel explains. Investigators theorized that cutting off certain domains within the isoforms would impact the localization and that a flow assay could be used as a read out for that. However, results showed that canonical isoform 1 does not appear to require its dimerization for translocation to take place, nor does it appear to require the first 10 amino acids, which are needed for dimerization and mitochondrial targeting, Figel concludes.