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Study of the laminin 111-derived peptide C16 internalization through endocytic vesicles and its possible exocytosis by breast cancer cells

Grant number: 19/24179-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): March 23, 2020
Effective date (End): September 22, 2020
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Ruy Gastaldoni Jaeger
Grantee:Maria Raquel Unterkircher Galheigo
Supervisor abroad: Alissa Margaret Weaver
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Vanderbilt University (VU), United States  
Associated to the scholarship:16/20228-4 - Interaction between the laminin-derived peptide C16 and beta 1 integrin in breast cancer cells. mechanisms involved and functional consequences, BP.DR

Abstract

Breast cancer is among the most frequent worldwide mortality. Tumor microenvironment undertakes important role during cancer progression. Different cells enmeshed in the extracellular matrix (ECM) compose such microenvironment. Laminin-111 is a major ECM glycoprotein and exhibits different bioactive peptides influencing tumor biology. We have demonstrated that the laminin-derived peptide C16 (KAFDITYVRLKF, short arm of gamma 1 chain) regulates migration, invasion, and invadopodia formation in different cancer cells. According to our previous results, the peptide C16 is endocytosed and directed to the endosome-lysosome pathway for degradation. This result, associated with the others, indicates that this peptide could be participating in integrins recycling pathway. Therefore, we propose to explore in more details peptide endocytosis through cell imaging using early and late endosome markers in breast cells treated with C16 conjugated with rhodamine. Moreover, we would like to know whether this peptide is found in extracellular vesicles using rhodamine-C16 and pHluorin_M153R-CD63, a reporter that allows the tracking of exosome secretion. This result will address whether internalized C16 is exocytosed from endosomes.