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Background CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. Methods The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFRβ was established in MDA-MB-231 cells to detect CDCP1 upon WHF treatment. Immunohistochemical staining was used to detect the expression of CDCP1 and PDGFRβ in TNBC clinical samples. Results We discovered that PDGF-BB-mediated activation of PDGFRβ increases CDCP1 protein expression through the downstream activation of ERK1/2. Inhibition of ERK1/2 activity reduced per se CDCP1 expression, evidence strengthening its role in CDCP1 expression regulation. Knock-down of PDGFRβ in TNBC cells impaired CDCP1 increase induced by WHF treatment, highlighting the role if this receptor as a central player of the WHF-mediated CDCP1 induction. A significant association between CDCP1 and PDGFRβ immunohistochemical staining was observed in TNBC specimens, independently of CDCP1 gene gain, thus corroborating the relevance of the PDGF-BB/PDGFRβ axis in the modulation of CDCP1 expression. Conclusion We have identified PDGF-BB/PDGFRβ–mediated pathway as a novel player in the regulation of CDCP1 in TNCBs through ERK1/2 activation. Our results provide the basis for the potential use of PDGFRβ and ERK1/2 inhibitors in targeting the aggressive features of CDCP1-positive TNBCs.

Wound healing fluid that originates from breast surgery increases the aggressiveness of cancer cells that remain after the surgery. We determined the effects of the extent of surgery and tumor-driven remodeling of the surrounding microenvironment on the ability of wound-healing to promote breast cancer progression. In our analysis of a panel of 34 cytokines, chemokines, and growth factors in wound healing fluid, obtained from 27 breast carcinoma patients after surgery, the levels of several small molecules were associated with the extent of cellular damage that was induced by surgery. In addition, the composition of the resulting wound healing fluid was associated with molecular features of the removed tumor. Specifically, IP-10, IL-6, G-CSF, osteopontin, MIP-1a, MIP-1b, and MCP1-MCAF were higher in more aggressive tumors. Altogether, our findings indicate that the release of factors that are induced by removal of the primary tumor and subsequent wound healing is influenced by the extent of damage due to surgery and the reactive stroma that is derived from the continuously evolving network of interactions between neoplastic cells and the microenvironment, based on the molecular characteristics of breast carcinoma cells.

Fibulin-1 (Fbln-1) is an immunogenic breast cancer-related glycoprotein identified by serological analysis of cDNA expression library (SEREX) strategy. Here, we show that dendritic cells from two breast cancer patients elicited a CD4 + -mediated T-cell response to Fbln-1 presentation. In both patients, an antibody response to Fbln-1 was also found. By contrast, a Fbln-1-seronegative patient and a weakly seropositive patient demonstrated no such T-cell response. Analysis of human breast cancers for Fbln-1 RNA and protein expression revealed the presence of Fbln-1C and -1D variants. Fbln-1 was detected in the cytoplasm and at the cell surface of different human breast carcinoma cell lines. Immunohistochemical analysis of 528 archival primary breast carcinomas showed the expression of Fbln-1 in 35% of the cases. When the immunohistochemical findings were compared against pathobiological information associated with each specimen, an inverse relationship between Fbln-1 and cathepsin D expression was observed ( P =0.04). Furthermore, even though long-term survival was similar between Fbln-1-positive and -negative cases, the survival of Fbln-1-positive cases improved when a lymphoid infiltrate was present at the tumour site. Taken together, our findings of an Fbln-1-specific immunity and the improved survival associated with Fbln-1 expression in the presence of lymphoid infiltration point to a role of Fbln-1 in tumour immunosurveillance.

Tyrosine phosphorylation is controlled by a balance of tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Whereas the contribution of PTKs to breast tumorigenesis is the subject of intense scrutiny, the potential role of PTPs is poorly known. RPTPalpha is implicated in the activation of Src family kinases, and regulation of integrin signaling, cell adhesion, and growth factor responsiveness. To explore its potential contribution to human neoplasia, we surveyed RPTPalpha protein levels in primary human breast cancer. We found RPTPalpha levels to vary widely among tumors, with 29% of cases manifesting significant overexpression. High RPTPalpha protein levels correlated significantly with low tumor grade and positive estrogen receptor status. Expression of RPTPalpha in breast carcinoma cells led to growth inhibition, associated with increased accumulation in G0 and G1, and delayed tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans.

CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. The expression of CDCP1, PDGFR[beta] and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFR[beta] was established in MDA-MB-231 cells to detect CDCP1 upon WHF treatment. Immunohistochemical staining was used to detect the expression of CDCP1 and PDGFR[beta] in TNBC clinical samples. We discovered that PDGF-BB-mediated activation of PDGFR[beta] increases CDCP1 protein expression through the downstream activation of ERK1/2. Inhibition of ERK1/2 activity reduced per se CDCP1 expression, evidence strengthening its role in CDCP1 expression regulation. Knock-down of PDGFR[beta] in TNBC cells impaired CDCP1 increase induced by WHF treatment, highlighting the role if this receptor as a central player of the WHF-mediated CDCP1 induction. A significant association between CDCP1 and PDGFR[beta] immunohistochemical staining was observed in TNBC specimens, independently of CDCP1 gene gain, thus corroborating the relevance of the PDGF-BB/PDGFR[beta] axis in the modulation of CDCP1 expression. We have identified PDGF-BB/PDGFR[beta]-mediated pathway as a novel player in the regulation of CDCP1 in TNCBs through ERK1/2 activation. Our results provide the basis for the potential use of PDGFR[beta] and ERK1/2 inhibitors in targeting the aggressive features of CDCP1-positive TNBCs.

Correction to: Oncogene (2004) 23, 2153–2160, doi: 10.1038/sj.onc.1207323 Published online 22 December 2003. Since publication of the above manuscript, the authors have identified an error in two of the author names. The correct names are William S Argraves and Waleed O Twal.

Background: Fibromyalgia, depression, and autoimmune diseases represent a triad of interconnected conditions characterized by overlapping biological pathways, including chronic inflammation, immune dysregulation, and neurochemical imbalances. Understanding their shared mechanisms offers opportunities for innovative therapeutic approaches. Objective: This systematic review explores the common inflammatory- and immune-related pathways among these conditions, emphasizing their implications for biomarker development and novel therapeutic strategies. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted in databases including PubMed, Scopus, Web of Science, and the Cochrane Library. Studies examining the relationship between fibromyalgia, depression, and autoimmune diseases with a focus on immune responses, inflammatory biomarkers, and therapeutic interventions were included. The quality of the selected studies was assessed using the Cochrane Risk of Bias tool. Results: From the 255 identified studies, 12 met the inclusion criteria. Evidence supports the role of pro-inflammatory cytokines (e.g., IL-6, TNF-α) and neurochemical dysregulation (e.g., serotonin, dopamine) as key factors in the pathophysiology of these conditions. Pilot studies highlight the potential of immune-modulating therapies, including low-dose IL-2 and anti-inflammatory agents such as N-acetylcysteine and minocycline, in alleviating both physical and psychological symptoms. Emerging biomarkers, including cytokine profiles and platelet serotonin activity, show promise for personalized treatment approaches. Conclusions: The shared inflammatory pathways linking fibromyalgia, depression, and autoimmune diseases underscore the need for integrated therapeutic strategies. Although pilot studies provide preliminary insights, validation through large-scale, multicenter trials is essential. Future research should focus on standardizing methodologies and leveraging biomarker-driven precision medicine to improve outcomes for patients with these complex, multifactorial conditions.