[en] Although lymph node (LN) metastasis is an important prognostic parameter in cervical cancer, the tissue remodeling at a pre-metastatic state is poorly documented in LNs. We here identified periostin (POSTN) as a component of non-metastatic LNs by applying proteomic analyses and computerized image quantifications on LNs of patients with cervical cancer. We provide evidence for remarkable modifications of POSTN and lymphatic vessel distributions and densities in non-metastatic sentinel and metastatic human LNs, when compared to distant non-metastatic LNs. POSTN deposition at a pre-metastatic stage was demonstrated in a pre-clinical murine model (the ear sponge assay). Its expression by fibroblastic LN cells was assessed by in situ hybridization and in vitro cultures. In vitro, POSTN promoted lymphatic endothelial cell functions and tumor cell proliferation. Accordingly, the in vivo injection of recombinant POSTN together with VEGF-C boosted the lymphangiogenic response, while the metastatic potential of tumor cells was drastically reduced using a POSTN blocking antibody. This translational study also supports the existence of an unprecedented dialog "in cascade", between the primary tumor and the first pelvic nodal relay in early cervical cancer, and subsequently from pelvic LN to para-aortic LNs in locally advanced cervical cancers. Collectively, this work highlights the association of POSTN deposition with lymphangiogenesis in LNs, and provides evidence for a key contribution of POSTN in promoting VEGF-C driven lymphangiogenesis and the seeding of metastatic cells.
Disciplines :
Oncology
Author, co-author :
Gillot, Lionel ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Lebeau, Alizée ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Baudin, Louis ; Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
POTTIER, Charles ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Louis, Thomas ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Durré, Tania ; Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
Longuespée, Rémi ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique ; Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] FWB - Fédération Wallonie-Bruxelles [BE] Fonds Léon Fredericq [BE] WELBIO - Institut wallon virtuel de recherche d'excellence dans les domaines des sciences de la vie [BE] Télévie [BE]
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