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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

900 - The Role of Neurotrophic Factors in Nerve-Cancer Crosstalk

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Anu Planken

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

A. Planken1, L. Truu2, K. Oselin1, V. Valvere1

Author affiliations

  • 1 Department Of Oncology And Hematology, North Estonia Medical Centre Foundation, 13419 - Tallinn/EE
  • 2 Department Of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn/EE
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Resources

Abstract 900

Background

"Nerve-cancer crosstalk" has been suggested as an important mechanism of tumor growth and dissemination. Cells in the cancer microenvironment secrete biomolecules which induce neoneurogenesis, while tumor cells utilize nerves for dissemination to other organs, thru a process of perineural invasion. The molecular basis for this crosstalk has remained unclear and no targeted approaches against these mechanisms exist. The current study evaluates the neuronal effects of cancer from the viewpoint of neurotrophic growth factors (NTFs). We screened various tumors for changes in gene expression of NTFs, in order to characterize the role of these factors in human cancers.

Methods

TNTF gene expression data was assesed from the Cancer Genome Atlas (TCGA) and GTEx transcriptomic databases for 33 cancers, totaling to 9736 tumor and 8587 normal samples. Data was analyzed by Gene Expression Profiling Interactive Analysis software (http://gepia.cancer-pku.cn/index.html), as transcripts per million using the log2 FC cutoff of 1 and by ANOVA. qRT-PCR for NTFs MANF and CDNF from patients with colorectal (CRC) and breast cancer (BC) was performed. Trizol and Qiagen RNeasy Mini Kit was used for RNA extraction, cDNA was synthesized using High Capacity cDNA RT-kit and TaqMan® qRT-PCR analysis was done with Roche LightCycler 480 system. Data was analyzed by the 2-ΔCT method and the unpaired Student t-test.

Results

The expression levels for the 3 NTFs: mesencephalic astrocyte-derived neurotrophic factor (MANF), cerebral dopamine neurotrophic factor (CDNF) and growth differentiation factor (GDF15) were profiled from the TCGA and GTEx databases. MANF RNA was upregulated in 9 different cancers, CDNF was up- in 1 and downregulated in 5 cancers and GDF15 was up- in 14 and downregulated in 3 cancers. qRT-PCR for MANF and CDNF from 52 patients with CRC showed that MANF is significantly upregulated 2-fold (p < 0.001) in CRC as compared to controls from the same patients, and upregulation was already seen in tumor-nearby samples. The analysis of RNA samples from 38 BC patients showed significant down-regulation for CDNF (p < 0.05).

Conclusions

These results support the hypothesis that NTFs indeed play a role in tumors and provide the basis for the need of further study for these factors within the cancer paradigm.

Clinical trial identification

Legal entity responsible for the study

Anu Planken.

Funding

The Archimedes Foundation.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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