Roland P. Bourette

Triple-negative breast cancer is an aggressive subtype of breast cancer that is not sensitive to hormone inhibition. Its treatment is mainly limited to conventional therapies, including neoadjuvant chemotherapy. But the acquisition of drug resistance is a major obstacle to the eradication of the tumor cells, especially the breast cancer stem cells (BCSCs). Using a double-transgenic mouse model 11.5 kb-GFP x C3(1)-Tag, we have previously shown that s-SHIP expression identifies a breast cancer stem cell–related population in primary tumors. To investigate the chemoresistance of s-SHIP/GFP-expressing tumor cells, we used the MAM326 cell line, established from a tumor isolated from these double-transgenic mice. A subset of s-SHIP/GFP+ MAM326 cells, displaying a drug-tolerant stem-related phenotype, exhibited enhanced resistance to various chemotherapy drugs, including paclitaxel and doxorubicin. Transcriptomic analysis revealed that these s-SHIP/GFP+ cells exhibited upregulation of several genes associated with chemoresistance. Furthermore, this analysis highlighted Pierce1 which plays a role in DNA damage response. We showed that Pierce1 was significantly overexpressed in transiently surviving cells treated with paclitaxel and doxorubicin, both in MAM326 cells and in a primary tumoroid model. Overexpression of PIERCE1 in human TNBC SUM159PT cells led to increased resistance to chemotherapy, while its knockdown reduced this resistance. Importantly, clinical data further supported the association of high PIERCE1 expression with poor prognosis and reduced survival in TNBC patients treated with neoadjuvant chemotherapy. This study unveils the potential of PIERCE1 as a therapeutic target for overcoming chemotherapy resistance in breast cancer.

Summary: Cancer surgery is a fundamental component of oncology treatment, its quality significantly impacts patient outcomes, influencing both relapse rates and survival. However, achieving this customization is contingent upon early collection of robust molecular data during surgery, providing accurate information for diagnosis, prognosis, and delineating surgical margins. The introduction of digital twin (DT) technology has recently opened a new era of precision and effectiveness in cancer surgery. Expanding from its successful implementations in the industrial sector, DT concept has evolved into a highly promising breakthrough in healthcare. Therefore, our study goal is on creating DT by using accurate and high-throughput molecular data obtained through mass spectrometry imaging. We developed a machine-learning-based pipeline that allow to depict infiltration of cancer cells into normal tissue that offer precise delineation of tumor margins thanks to SpiderMass. This process also enables the prediction of relative presence of bacterial strains in tumoral and healthy mammary glands.

Therapies reconstituting autologous antiviral immunocompetence may represent an important prophylaxis and treatment for immunosuppressed individuals. Following hematopoietic cell transplantation (HCT), patients are susceptible to Herpesviridae including cytomegalovirus (CMV). We show in a murine model of HCT that macrophage colony‐stimulating factor (M‐CSF) promoted rapid antiviral activity and protection from viremia caused by murine CMV. M‐CSF given at transplantation stimulated sequential myeloid and natural killer (NK) cell differentiation culminating in increased NK cell numbers, production of granzyme B and interferon‐γ. This depended upon M‐CSF‐induced myelopoiesis leading to IL15Rα‐mediated presentation of IL‐15 on monocytes, augmented by type I interferons from plasmacytoid dendritic cells. Demonstrating relevance to human HCT, M‐CSF induced myelomonocytic IL15Rα expression and numbers of functional NK cells in G‐CSF‐mobilized hematopoietic stem and progenitor cells. Together, M‐CSF‐induced myelopoiesis triggered an integrated differentiation of myeloid and NK cells to protect HCT recipients from CMV. Thus, our results identify a rationale for the therapeutic use of M‐CSF to rapidly reconstitute antiviral activity in immunocompromised individuals, which may provide a general paradigm to boost innate antiviral immunocompetence using host‐directed therapies.

Prostate cancer is a major public health concern and one of the most prevalent forms of cancer worldwide. The definition of altered signaling pathways implicated in this complex disease is thus essential. In this context, abnormal expression of the receptor of Macrophage Colony-Stimulating Factor-1 (M-CSF or CSF-1) has been described in prostate cancer cells. Yet, outcomes of this expression remain unknown. Using mouse and human prostate cancer cell lines, this study has investigated the functionality of the wild-type CSF-1 receptor in prostate tumor cells and identified molecular mechanisms underlying its ligand-induced activation. Here, we showed that upon CSF-1 binding, the receptor autophosphorylates and activates multiple signaling pathways in prostate tumor cells. Biological experiments demonstrated that the CSF-1R/CSF-1 axis conferred significant advantages in cell growth and cell invasion in vitro. Mouse xenograft experiments showed that CSF-1R expression promoted the aggressiveness of prostate tumor cells. In particular, we demonstrated that the ligand-activated CSF-1R increased the expression of spp1 transcript encoding for osteopontin, a key player in cancer development and metastasis. Therefore, this study highlights that the CSF-1 receptor is fully functional in a prostate cancer cell and may be a potential therapeutic target for the treatment of prostate cancer.

Breast cancer is a major public health problem and the leading world cause of women death by cancer. Both the recurrence and mortality of breast cancer are mainly caused by the formation of metastasis. The long non-coding RNA H19, the precursor of miR-675, is involved in breast cancer development. The aim of this work was to determine the implication but, also, the relative contribution of H19 and miR-675 to the enhancement of breast cancer metastatic potential. We showed that both H19 and miR-675 increase the invasive capacities of breast cancer cells in xenografted transgenic zebrafish models. In vitro, H19 and miR-675 enhance the cell migration and invasion, as well as colony formation. H19 seems to induce the epithelial-to-mesenchymal transition (EMT), with a decreased expression of epithelial markers and an increased expression of mesenchymal markers. Interestingly, miR-675 simultaneously increases the expression of both epithelial and mesenchymal markers, suggesting the induction of a hybrid phenotype or mesenchymal-to-epithelial transition (MET). Finally, we demonstrated for the first time that miR-675, like its precursor H19, increases the stemness properties of breast cancer cells. Altogether, our data suggest that H19 and miR-675 could enhance the aggressiveness of breast cancer cells through both common and different mechanisms.

Synuclein gamma expression enhances radiation resistance of breast cancer cells Synuclein gamma expression enhances radiation resistance of breast cancer cells

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Guillaume Brocqueville1, Renee S. Chmelar2, Hélène Bauderlique-Le Roy1, Emeric Deruy3, Lu Tian1, Robert L. Vessella4, Norman M. Greenberg2, 5, Larry R. Rohrschneider2, *, Roland P. Bourette1 1University of Lille, CNRS, Institut Pasteur de Lille, UMR 8161-M3T-Mechanisms of Tumorigenesis and Targeted Therapies, SIRIC ONCOLille, F-59000 Lille, France 2Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 3BioImaging Center Lille, Institut Pasteur de Lille, University of Lille, F-59000 Lille, France 4Department of Urology, University of Washington, Seattle, WA 98195, USA 5Present address: NMG Scientific Consulting, North Potomac, MD 20878, USA *Deceased Correspondence to: Roland P. Bourette, e-mail: roland.bourette@ibl.cnrs.fr Keywords: stem cells, prostate, s-SHIP, epithelial cells, transgenic mouse Received: November 04, 2015 Accepted: March 28, 2016 Published: April 12, 2016

H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b