Purinergic signaling in the phenotypic transition of Tumor Associated Macrophages (TAMs) and Circulating Tumor Cells (CTCs) to Breast Cancer brain metastasis

• Grant number: 22/11093-9
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: Claudiana Lameu
• Grantee: Claudiana Lameu
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alexander Henning Ulrich ; Ludmilla Thomé Domingos Chinen ; Talita Glaser

Abstract

Triple-negative breast cancer (TNBC) is the most invasive among all subtypes, and 46% of patients have metastasis reducing their survival rate. To metastasize, tumor cells need to separate from the tissue of origin and reach the circulation, becoming circulating tumor cells (CTCs). CTCs then need to survive and colonize metastatic sites. In the case of brain metastasis, TNBC cells, in addition to being able to cross the bloodbrain barrier, must establish a favorable phenotype for colonization, a phenomenon called breast-brain transition that produces cells mimicking GABAergic neurons. For undergo this complex process, tumor cells associate with tumor-associated macrophages (TAMs). The high phenotypic plasticity of macrophages in response to the microenvironment, in which they are found, favors immunotherapeutic approaches of re-educating the population that presents a pro-tumor phenotype to an antitumor phenotype, thus promoting the immune response against the tumor. This prevents CTCs from circulating in the blood and blocks the phenotypic transition that allows brain metastasis. We propose to study P2X7 and P2Y2 receptors in the phenotypic transition mechanisms of CTCs and TAMs, which turns the cancer more aggressive and colonizable in the brain. Thus, the project has the potential to reveal the mechanisms of interaction of CTCs and TAMs in the metastasis process as well as to propose a new immunotherapeutic strategy based on the phenotypic modulation of TAMs. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NUNEZ-RIOS, J. D.; ULRICH, H.; DIAZ-MUNOZ, M.; LAMEU, C.; VAZQUEZ-CUEVAS, F. G.. Purinergic system in cancer stem cells. PURINERGIC SIGNALLING, v. N/A, p. 16-pg., 2023-11-15. (22/11093-9)

COUTINHO, FERNANDA; GUIMARAES, LARA M. F.; SEEGER, RODRIGO; SANTOS, ANA PAULA J.; GLASER, TALITA; YAMAMOTO, DENISE; LACERDA, LUCAS; ARNAUD-SAMPAIO, VANESSA; ROSSINI, CAIO V. T.; RABELO, IZADORA; et al. Bj-PRO-10c, as an allosteric regulator of argininosuccinate synthase, is a potential therapy for neuroblastoma metastasis. Toxicon, v. 233, p. 9-pg., 2023-09-01. (13/07937-8, 16/11098-0, 18/18799-9, 19/17483-0, 15/19128-2, 22/11093-9, 19/08999-3, 18/07366-4)

MOL PEREIRA, ERIKA A.; SANTOS, M. SOLEDADE C. S.; MINAS DA PIEDADE, MANUEL E.; FARIA, RAFAEL DE OLIVEIRA; DE SOUZA, GABRIEL BATISTA; LAMEU, CLAUDIANA; BARBOSA, EDUARDO JOSE; BOU-CHACRA, NADIA A.; LOURENCO, FELIPE REBELLO; NONATO BEZZON, VINICIUS DANILO; et al. Biosurfactants as stabilizers of niclosamide nanocrystals: Enhancing stability, solubility, and cytotoxicity profiling. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 100, p. 11-pg., 2024-08-27. (22/11093-9, 21/04769-3, 19/04998-2)

BENTO, CAROLINA ADRIANE; ARNAUD-SAMPAIO, VANESSA FERNANDES; GLASER, TALITA; ADINOLFI, ELENA; COUTINHO-SILVA, ROBSON; ULRICH, HENNING; LAMEU, CLAUDIANA. P2X7 receptor in macrophage polarization and its implications in neuroblastoma tumor behavior. PURINERGIC SIGNALLING, v. N/A, p. 18-pg., 2024-10-19. (18/14993-5, 22/11093-9, 18/07366-4, 15/19128-2)