Neurotrophin receptors - prognostic markers and therapeutic targets for HNSCC?

Neurotrophins bind to Trk receptors (tropomyosin receptor kinase) and with lower affinity to CD271. These receptors are expressed in the nervous system, a variety of carcinomas and in the mucosa of the upper aerodigestive tract. This study investigated the expression and function of these receptors in head and neck squamous cell carcinomas (HNSCCs).

We investigated the receptor expression patterns in 184 human HNSCC samples. Clinical data and survival were analyzed. Their relevance for proliferation, migration, anoikis resistance and sphere formation was investigated in vitro. Tumor cells were grouped by FACS sorting according to their receptor expression strength. The CD271 inhibitor LMA11A31 dihydrochloride and the Trk inhibitor PF-06273340 were tested.

The majority of the tumors expressed CD271 and TrkA. Only half of the tumors were positive for TrkB and TrkC. A high CD271 expression was associated with a poor prognosis and distant metastases, the expression of the Trks indicated lower tumor differentiation (G status). In the cell lines, a high CD271 expression marked fast proliferating cells. When CD271 and TrkC were coexpressed, tumor cells showed a reduced proliferation rate in-vitro. LM11A31 suppressed migration in one of three cell lines. PF06273340 and the neurotrophins had no effect on migration. None of the neurotrophins and inhibitors had an effect on the proliferation. Neurotrophins promoted anoikis resistance and sphere formation.

We conclude that CD271 and Trks can provide prognostic information for HNSCC. CD271 may be a therapeutic target to prevent metastasis.

partially published in: Foerster Y, et al. Relevance of Neurotrophin Receptors CD271 and TrkC for Prognosis, Migration, and Proliferation in Head and Neck Squamous Cell Carcinoma. Cells2019; 8(10).

Poster-PDF A-1166.PDF

Publication History

Article published online:
10 June 2020