Metastatic progression in experimental and spontaenous animal cancer models

The goal of the project is the study of the metastatic cascade in spontaneous feline, canine and human cancer to overcome limitations due to induced cancer models. In the context of a personalized cancer medicine, in vitro studies on tumor organoids and in vivo mouse model of metastases with feline, canine, and human cell lines are included. The specific aims are i) to compare results from traditional tissue matrixes such as paraffin-embedded and fresh tissues with those from innovative in vitro derived samples (organoids), ii) to deeper understand the intra- and inter-species value of the models, and iii) to elucidate the presence of a “core set” of genes, and related signaling pathways, implicated in tumorigenesis and clinical outcome, which would represent potential therapeutic targets. The idea is to examine the genome and trascriptome signatures of non-metastatic and metastastic tumors and of the paired metastastes by whole-exome sequencing and RNA sequencing. Non-tumoral control tissues will also be included. Samples collection will include highly metastatic cancer types such as hormone receptors negative mammary cancer, melanoma, hemangiosarcoma, mast cell tumor, osteosarcoma. Quantitatively significant and homogeneous sample groups will be included in the analyses. Human samples will be either obtained by active collaborations or as genetic data from human organoid/cancer databases to better define similarities and differences between the species.

Five publications related to the Research Topic for the interview:

  1. 1: Munchel S, Hoang Y, Zhao Y, Cottrell J, Klotzle B, Godwin AK, Koestler D, Beyerlein P, Fan JB, Bibikova M, Chien J. Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics. Oncotarget. 2015 Sep 22;6(28):25943-61. doi: 10.18632/oncotarget.4671. PubMed PMID: 26305677; PubMed Central PMCID: PMC4694877.
  2. Krøigård AB, Larsen MJ, Lænkholm AV, Knoop AS, Jensen JD, Bak M, Mollenhauer J, Thomassen M, Kruse TA. Identification of metastasis driver genes by massive parallel sequencing of successive steps of breast cancer progression. PLoS One. 2018 Jan 2;13(1):e0189887. doi: 10.1371/journal.pone.0189887. eCollection 2018. PubMed PMID: 29293529; PubMed Central PMCID: PMC5749725.
  3. Johnstone CN, Pattison AD, Gorringe KL, Harrison PF, Powell DR, Lock P, Baloyan D, Ernst M, Stewart AG, Beilharz TH, Anderson RL. Functional and genomic characterization of a xenograft model system for the study of metastasis in triple-negative breast cancer. Dis Model Mech. 2018 Apr 30. pii: dmm.032250. doi: 10.1242/dmm.032250. [Epub ahead of print] PubMed PMID: 29720474.
  4. Brian W. Davis Elaine A. Ostrander Domestic Dogs and Cancer Research: A Breed-Based Genomics Approach ILAR Journal, Volume 55, Issue 1, 1 January 2014, Pages 59–68, https://doi.org/10.1093/ilar/ilu017
  5. Robert Klopfleisch, Dido Lenze, Michael Hummel and Achim D Gruber Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles. BMC Cancer 2010 10:618