An EMILIN1-negative microenvironment promotes tumor cell proliferation and lymph node invasion

Carla Danussi, Alessandra Petrucco, Bruna Wassermann, Teresa Maria Elisa Modica, Eliana Pivetta, Lisa Del Bel Belluz, Alfonso Colombatti, Paola Spessotto

Research output: Contribution to journalArticle

Abstract

The evidence that EMILIN1 (Elastic Microfibril Interface Located proteIN) deficiency in Emilin1-/- mice caused dermal and epidermal hyperproliferation and an abnormal lymphatic phenotype prompted us to hypothesize the involvement of this extracellular matrix component in tumor development and in lymphatic metastasis. Using the 12-dimethylbenz(α) anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) two-stage model of skin carcinogenesis, we found that Emilin1-/- mice presented an accelerated formation, a higher incidence, and the development of a larger number of tumors compared with their wild-type littermates. EMILIN1-negative tumors showed more Ki67-positive proliferating cells and higher levels of pErk1/2. In these tumors, PTEN expression was lower. Emilin1-/- mice displayed enhanced lymphangiogenesis both in the tumor and in the sentinel lymph nodes. Accordingly, tumor growth and lymph node metastasis of transplanted syngenic tumors were also increased in Emilin1-/- mice. In vitro transmigration assays through lymphatic endothelial cells showed that EMILIN1 deficiency greatly facilitated tumor cell trafficking. Overall, these data established that EMILIN1 exerts a protective role in tumor growth, in tumor lymphatic vessel formation, as well as in metastatic spread to lymph nodes and reinforced the importance of its presence in the microenvironment to determine the tumor phenotype.

Original languageEnglish
Pages (from-to)1131-1143
Number of pages13
JournalCancer Prevention Research
Volume5
Issue number9
DOIs
Publication statusPublished - Sep 2012

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Danussi, C., Petrucco, A., Wassermann, B., Modica, T. M. E., Pivetta, E., Del Bel Belluz, L., Colombatti, A., & Spessotto, P. (2012). An EMILIN1-negative microenvironment promotes tumor cell proliferation and lymph node invasion. Cancer Prevention Research, 5(9), 1131-1143. https://doi.org/10.1158/1940-6207.CAPR-12-0076-T