Proteasomes in Patient Rectal Cancer and Different Intestine Locations: Where Does Proteasome Pool Change?

Simple Summary: One of the most complicated problems during rectal cancer surgery is to determine what part of intestine to remove along with tumor. If the excised fragment will be too small, it could increase the risk of tumor recurrence. On the contrary, the removal of extra tissues could be completely unnecessary and complicate patient life a lot, especially when the region is close to sphincter. To determine the length of fragments to remove, it was necessary to reveal areas without changes in molecule functioning, specific for tumor. We investigated functioning the proteasomes, important cellular components, in patient rectal cancer and different intestine locations and did not reveal tumor-specific characteristics of proteasomes at sphincter side of intestine even at a distance of 2-4 cm from the tumor. This result supports the idea of preserving the sphincter under surgery. Besides, we discovered proteasome subtype that may be a promising target for anti-cancer therapy. A special problem in the surgery of rectal cancer is connected with a need for appropriate removal of intestine parts, along with the tumor, including the fragment close to the sphincter. To determine the length of fragments to remove, it is necessary to reveal areas without changes in molecule functioning, specific for tumor. The purpose of the present study was to investigate functioning the proteasomes, the main actors in protein hydrolysis, in patient rectal adenocarcinoma and different intestine locations. Chymotrypsin-like and caspase-like activities, open to complex influence of different factors, were analyzed in 43-54 samples by Suc-LLVY-AMC- and Z-LLE-AMC-hydrolysis correspondingly. Both activities may be arranged by the decrease in the location row: cancer -> adjacent tissue -> proximal (8-20 cm from tumor) and distal (2 and 4 cm from tumor) sides. These activities did not differ noticeably in proximal and distal locations. Similar patterns were detected for the activities and expression of immune subunits LMP2 and LMP7 and expression of 19S and PA28 alpha beta activators. The largest changes in tumor were related to proteasome subtype containing LMP2 and PA28 alpha beta that was demonstrated by native electrophoresis. Thus, the results indicate a significance of subtype LMP2-PA28 alpha beta for tumor and absence of changes in proteasome pool in distal fragments of 2-4 cm from tumor.

Automated summary

In rectal cancer surgery, determining the appropriate length of intestine parts to remove along with the tumor is crucial. Research showed that there is no tumor-specificity in proteasome genes at the sphincter side of the intestine 2-4 cm away from the tumor, supporting sphincter preservation. Additionally, a proteasome subtype with potential as a target for anti-cancer therapy was discovered.