title: An EMILIN1-negative microenvironment promotes tumor cell proliferation and lymph node invasion.
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.
authors: Experimental Oncology 2, CROO-IRCCS, National Cancer Institute, Aviano, Via Franco Gallini, 2, Aviano 33081, Italy.
authors: Carla
authors: C
authors: Danussi
authors: Alessandra
authors: A
authors: Petrucco
authors: Bruna
authors: B
authors: Wassermann
authors: Teresa Maria Elisa
authors: TM
authors: Modica
authors: Eliana
authors: E
authors: Pivetta
authors: Lisa
authors: L
authors: Del Bel Belluz
authors: Alfonso
authors: A
authors: Colombatti
authors: Paola
authors: P
authors: Spessotto
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; C030340:elastin microfibril interface located protein