bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022‒01‒23
three papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

  1. Cells. 2022 Jan 14. pii: 280. [Epub ahead of print]11(2):
      Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 played a role in this process. Through immunohistochemistry on human tissue microarrays, we showed that NLGN1 is expressed by prostatic and pancreatic cancer tissues in discrete stages and tumor districts. Next, we performed in vitro and in vivo assays, demonstrating that NLGN1 promotes cancer cell invasion and migration along nerves. Because of the established role of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) in tumor-nerve interactions, we assessed a potential NLGN1-GDNF cooperation. We found that blocking GDNF activity with a specific antibody completely inhibited NLGN1-induced in vitro cancer cell invasion of nerves. Finally, we demonstrated that, in the presence of NLGN1, GDNF markedly activates cofilin, a cytoskeletal regulatory protein, altering filopodia dynamics. In conclusion, our data further prove the existence of a molecular and functional cross-talk between the nervous system and cancer cells. NLGN1 was shown here to function along one of the most represented neurotrophic factors in the nerve microenvironment, possibly opening new therapeutic avenues.
    Keywords:  cofilin; filopodia; glial cell line-derived neurotrophic factor; neuroligin 1; tumor–nervous connections
  2. Hum Pathol. 2022 Jan 18. pii: S0046-8177(22)00013-2. [Epub ahead of print]
      Perineural invasion (PNI) by prostate cancer detected on systematic sextant biopsy (S-Bx) has been considered as a key prognosticator. However, the clinical significance of PNI on MRI-targeted biopsy (T-Bx) needs to be further investigated. We assessed 169 patients undergoing T-Bx with concurrent S-Bx, followed by radical prostatectomy (RP) from 2015-2019. In all cases where cancer was detected on T-Bx only (n=34) or both S-Bx and T-Bx (B-Bx; n=135), PNI was found in 33 (19.5%) T-Bxs. Compared with no PNI, PNI on T-Bx was associated with higher Grade Group on biopsy/RP, higher pT stage, and lymph node metastasis. Outcome analysis revealed a significant difference in the risk of biochemical recurrence after RP between cases with vs. without PNI on T-Bx (P=0.021). Next, in the 135 B-Bx cases, PNI was found on S-Bx only (n=31), T-Bx only (n=15), or B-Bx (n=16). Compared with PNI on S-Bx, B-Bx PNI was associated with higher preoperative prostate-specific antigen, higher biopsy GG, higher pT stage, and larger tumor volume. There were no significant differences in any of the clinicopathologic features examined between cases with PNI on T-Bx only vs. B-Bx. Moreover, in this subgroup of patients, PNI on B-Bx was associated with significantly higher risks of biochemical recurrence, compared with PNI on S-Bx only (P=0.024) or T-Bx only (P=0.033). In multivariate analysis, PNI on B-Bx showed significance for recurrence (HR=2.787, P=0.034). The presence of PNI on T-Bx, particularly B-Bx, associated with worse histopathologic features on RP and poorer outcomes might thus be useful for risk stratification.
    Keywords:  Perineural invasion; Prognosis; Prostate cancer; Radical prostatectomy; Sextant biopsy; Targeted biopsy