44P - Role of ICAM-1/LFA-1 interaction in the angiogenic and desmoplasic response in Liver metastasis

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer biology
Basic Scientific Principles
Presenter Alba Alonso
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors A. Alonso, I. Romayor, A. Benedicto, I. Hernandez-Unzueta, J. Marquez, B. Arteta
  • Cell Biology And Histology, Faculty Of Medicine And Nursery, Universidad del País Vasco UPV/EHU, 48940 - Leioa/ES



The colorectal cancer is one of the most common cancers in the world being the main cause of death the metastatic spread to the liver. During metastatic progression, a stromal and tumor cell crosstalk mediated by hepatic ICAM-1 and tumor LFA-1 interaction modulate the tumor microenvironment through an inflammatory and immune response. Additionally, a matrix remodeling and angiogenic response is also associated with tumor progression. The main cell type associated to these processes is the fibroblast associated to the tumor. Thus, the aim of this work is to elucidate the effect of ICAM-1/LFA-1 interaction during the angiogenic and desmoplasic response during liver metastatic progression.


To do so, the effect of ICAM-1/LFA-1 interaction on the tumor progression and recruitment of cancer associated fibroblasts was analyzed by an experimental metastasis assay in vivo and a modified Boyden chamber migration assays in vitro, after either activation of tumor cells with sICAM-1 or blocking of ICAM-1/FA-1 interaction. In addition, the effects of LFA-1 tumor depletion on tumor migratory potential induced by tumor-activated fibroblasts derived factors were analyzed. Also, the effect of the modulation of this pathway on MMPs protein and angiogenic gene expression levels was measured by zymography and qPCR, respectively.


In vivo and in vitro assays showed an increase on fibroblast and tumor cells recruitment after activation of tumor LFA-1 activation by binding with sICAM-1 which was abrogated after blocking of LFA-1. Moreover, the expression levels of MMPS and other proangiogenic factors were decrease after the blockage of ICAM-1/LFA-1 interaction. Also, the collagen deposition was increased after LFA-1 activation and diminished by LFA-1 blocking.


The interaction of ICAM-1 with tumor LFA-1 favors the recruitment of fibroblast within the tumor mediated by a modulation of pro-desmoplasic factors. This favors the remodeling of the tumor stroma and the angiogenic response and promotes tumor metastatic progression. Thus, LFA-1ICAM-1 interaction might be pointed out as a potential target for therapy of the metastatic disease.

Clinical trial identification

Legal entity responsible for the study

Department of Cellular Biology and Histology, University of the Basque Country, School of Medicine and Nursery


Basque Government


All authors have declared no conflicts of interest.