FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).

While preclinical studies consistently implicate FGFR‑signalling in breast cancer (BC) progression, clinical evidence fails to support these findings. It may be that the clinical significance of FGFR ought to be analysed in the context of the stroma, activating or repressing its function. The present review aimed to provide such a context by summarizing the existing data on the prognostic and/or predictive value of selected cancer‑associated fibroblasts (CAFs)‑related factors, that either directly or indirectly may affect FGFR‑signalling.

FGFR2-triggered autophagy and activation of Nrf-2 reduce breast cancer cell response to anti-ER drugs.

Background: Genetic abnormalities in the FGFR signalling occur in 40% of breast cancer (BCa) patients resistant to anti-ER therapy, which emphasizes the potential of FGFR-targeting strategies. Recent findings indicate that not only mutated FGFR is a driver of tumour progression but co-mutational landscapes and other markers should be also investigated. Autophagy has been recognized as one of the major mechanisms underlying the role of tumour microenvironment in promotion of cancer cell survival, and resistance to anti-ER drugs.

FGFR4-driven plasticity in breast cancer progression and resistance to therapy.

Breast cancer (BCa) is a complex and heterogeneous disease, with different intrinsic molecular subtypes that have distinct clinical outcomes and responses to therapy. Although intrinsic subtyping provides guidance for treatment decisions, it is now widely recognised that, in some cases, the switch of the BCa intrinsic subtype (which embodies cellular plasticity), may be responsible for therapy failure and disease progression. Aberrant FGFR4 signalling has been implicated in various cancers, including BCa, where it had been shown to be associated with aggressive subtypes, such as HER2-enriched BCa, and poor prognosis.

Liver metastasis or a pseudocyst? A rare presentation of leiomyosarcoma's metastasis in the liver.

Gastrointestinal neoplasms most commonly metastasize to the liver, where they are typically found as solid and hypervascular lesions. Here, we describe a case of a 44-year-old man with a leiomyosarcoma of the rectum, who at the time of diagnosis presented with a small (5 mm in diameter) cyst-like lesion in the liver. Positron emission tomography demonstrated no increased metabolism in the area of the cyst, suggesting a benign character of the lesion.

FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer.

We have recently demonstrated that fibroblast growth factor receptor 2 (FGFR2)-mediated signalling alters progesterone receptor (PR) activity and response of oestrogen receptor α (ER)-positive (ER+) breast cancer (BCa) cell lines to anti-ER agents. Little is known about whether the crosstalk between ER and PR, shown to be modulated by the hormonal background, might also be affected by FGFR2. Here, PR-dependent behaviour of ER+ BCa cells was studied in the presence of oestrogen (E2) and progesterone (P4) and/or FGF7.

Subtype-Specific Tumour Immune Microenvironment in Risk of Recurrence of Ductal Carcinoma In Situ: Prognostic Value of HER2.

Increasing evidence suggests that the significance of the tumour immune microenvironment (TIME) for disease prognostication in invasive breast carcinoma is subtype-specific but equivalent studies in ductal carcinoma in situ (DCIS) are limited. The purpose of this paper is to review the existing data on immune cell composition in DCIS in relation to the clinicopathological features and molecular subtype of the lesion. We discuss the value of infiltration by various types of immune cells and the PD-1/PD-L1 axis as potential markers of the risk of recurrence.

Adenoid cystic carcinoma of the breast - an uncommon malignancy with unpredictable clinical behaviour. A case series of three patients.

Adenoid cystic carcinoma (AdCC) is a common tumour of the minor salivary gland, rarely seen in other anatomical locations. In particular, AdCC of the breast accounts for < 0.1% of patients diagnosed with breast cancer.

The diagnostic challenge in pulmonary tumour embolism in cancer: a case report and literature review.

Pulmonary tumour embolism is a rare condition without specific symptoms or pathognomonic features. Pulmonary tumour embolism can occur as the first manifestation of cancer, but because of diagnostic difficulties, it is often wrongly recognised as a more common cardiopulmonary disease. We present a case of a 46-year-old Caucasian male with no prior malignancy diagnosis, admitted because of progressing dyspnoea and cough.

A 'Real-Life' Experience on Automated Digital Image Analysis of FGFR2 Immunohistochemistry in Breast Cancer.

We present here an assessment of a 'real-life' value of automated machine learning algorithm (AI) for examination of immunohistochemistry for fibroblast growth factor receptor-2 (FGFR2) in breast cancer (BC). Expression of FGFR2 in BC ( = 315) measured using a certified 3DHistech CaseViewer/QuantCenter software 2.3.

Upregulation of HIF1-α via an NF-κB/COX2 pathway confers proliferative dominance of HER2-negative ductal carcinoma in situ cells in response to inflammatory stimuli.

There are data to suggest that some ductal carcinoma in situ (DCIS) may evolve through an evolutionary bottleneck, where minor clones susceptible to the imposed selective pressure drive disease progression. Here, we tested the hypothesis that an impact of the inflammatory environment on DCIS evolution is HER2-dependent, conferring proliferative dominance of HER2-negative cells. In tissue samples, density of tumour-infiltrating immune cells (TIICs) was associated only with high tumour nuclear grade, but in 9% of predominantly HER2-negative cases, the presence of tumoral foci ('hot-spots') of basal-like cells with HIF1-α activity adjacent to the areas of dense stromal infiltration was noted.

Hormonal Receptor Status Determines Prognostic Significance of FGFR2 in Invasive Breast Carcinoma.

Interaction between fibroblast growth factor receptor 2 (FGFR2) and estrogen/progesterone receptors (ER/PR) affects resistance to anti-ER therapies, however the prognostic value of FGFR2 in breast cancer (BCa) remains largely unexplored. We have recently showed in vitro that FGFR2-mediated signaling alters PR activity and response to anti-ER treatment. Herein, prognostic significance of FGFR2 in BCa was evaluated in relation to both ER/PR protein status and a molecular signature designed to reflect PR transcriptional activity.

Tetraspanin CD151 impairs heterodimerization of ErbB2/ErbB3 in breast cancer cells.

CD151/Tspan24 (SFS-1, PETA3) is one of the best characterized members of the tetraspanin family, whose involvement in breast cancer (BCa) progression was demonstrated both in vitro and in vivo. We have recently reported that in ErbB2-overexpressing BCa cells grown in 3D laminin-rich extracellular matrix, CD151 regulated basal phosphorylation and homodimerization of ErbB2 and sensitized the cells to Herceptin (trastuzumab). Following from these data, we have here analyzed an involvement of CD151 in regulation of ErbB2/ErbB3 heterodimerization and its impact on cell response to Herceptin.

RSK1 promotes murine breast cancer growth and metastasis.

Introduction: Triple-negative breast cancer (TNBC), representing over 15% of all breast cancers, has a poorer prognosis than other subtypes. There is no effective targeted treatment available for the TNBC sufferers. Ribosomal S6 kinases (RSKs) have been previously proposed as drug targets for TNBC based on observations that 85% of these tumors express activated RSKs.

Progesterone impairs Herceptin effect on breast cancer cells.

Breast cancer (BCa) is the most common cancer affecting women worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in ~20-25% of invasive ductal breast carcinomas and is associated with the more aggressive phenotype. Herceptin, a humanized antibody against HER2, is a standard therapy in HER2-overexpressing cases.

FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells.

Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen.

Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation.

The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9.

Fibroblast growth factor signalling induces loss of progesterone receptor in breast cancer cells.

We have recently demonstrated that, fibroblast growth factor 2 (FGFR2), signalling via ribosomal S6 kinase 2 (RSK2), promotes progression of breast cancer (BCa). Loss of progesterone receptor (PR), whose activity in BCa cells can be stimulated by growth factor receptors (GFRs), is associated with poor patient outcome. Here we showed that FGF7/FGFR2 triggered phosphorylation of PR at Ser294, PR ubiquitination and subsequent receptor`s degradation via the 26S proteasome pathway in BCa cells.

Interactions between FGFR2 and RSK2-implications for breast cancer prognosis.

We have previously demonstrated that fibroblast growth factor receptor 2 (FGFR2) activates ribosomal s6 kinase 2 (RSK2) in mammary epithelial cells and that this pathway promotes in vitro cell growth and migration. Potential clinical significance of FGFR2 and RSK2 association has never been investigated. Herein, we have undertaken an evaluation of a possible relationship between FGFR2/RSK2 interdependence and disease outcome in breast cancer (BCa) patients.

[Aspects of progesterone receptor (PR) activity regulation - impact on breast cancer progression].

Progesterone receptor (PR) and its specific ligand play a key role in development and physiology of mammary gland. The role of PR in initiation and progression of breast carcinoma (BCa) is unquestionable, although molecular mechanism of PR action is complex and not fully understood. It is known that increased risk of breast cancer is associated with progestin-based (synthetic ligands of progesterone) hormonal contraception or hormone replacement therapies.

Expression of CD151/Tspan24 and integrin alpha 3 complex in aid of prognostication of HER2-negative high-grade ductal carcinoma in situ.

The pro-tumorigenic and pro-metastatic functions of the tetraspanin protein CD151 (Tspan24) are thought to be dependent on its ability to form complexes with laminin-binding integrin receptors (i.e. alpha6beta1, alpha3beta1, alpha6beta4).

Lack of CD151/integrin α3β1 complex is predictive of poor outcome in node-negative lobular breast carcinoma: opposing roles of CD151 in invasive lobular and ductal breast cancers.

Background: The proposed involvement of CD151 in breast cancer (BCa) progression is based on findings from studies in invasive ductal carcinoma (IDC). The IDC and invasive lobular carcinoma (ILC) represent distinct disease entities. Here we evaluated clinical significance of CD151 alone and in association with integrin α3β1 in patients with ILC in context of the data of our recent IDC study.

Phosphorylation of RSK2 at Tyr529 by FGFR2-p38 enhances human mammary epithelial cells migration.

The members of p90 ribosomal S6 kinase (RSK) family of Ser/Thr kinases are downstream effectors of MAPK/ERK pathway that regulate diverse cellular processes including cell growth, proliferation and survival. In carcinogenesis, RSKs are thought to modulate cell motility, invasion and metastasis. Herein, we have studied an involvement of RSKs in FGF2/FGFR2-driven behaviours of mammary epithelial and breast cancer cells.

CD151 in cancer progression and metastasis: a complex scenario.

Originally identified as a molecular organizer of interacting proteins into tetraspanin-enriched microdomains, the tetraspanin CD151 has now been shown to be involved in tumour progression. Increasing evidence emerging from in vitro, in vivo and clinical analyses implicates this tetraspanin in supporting growth of various types of tumours at different levels. It affects both cell autonomous behavior and communication with neighboring cells and the microenvironment.

Tetraspanins in human epithelial malignancies.

Transmembrane proteins of the tetraspanin superfamily are implicated in a broad spectrum of cellular processes in many biological systems in both health and disease. Tetraspanins form specialized membrane microdomains on the cell surface which control cell proliferation and migration through various adhesion and growth factor receptors. Recent extensive research has shown that expression of various tetraspanins and their associated partners is deregulated in human malignancies.

Nuclear magnetic resonance detects phosphoinositide 3-kinase/Akt-independent traits common to pluripotent murine embryonic stem cells and their malignant counterparts.

Pluripotent embryonic stem (ES) cells, a potential source of somatic precursors for cell therapies, cause tumors after transplantation. Studies of mammalian carcinogenesis using nuclear magnetic resonance (NMR) spectroscopy have revealed changes in the choline region, particularly increased phosphocholine (PCho) content. High PCho levels in murine ES (mES) cells have recently been attributed to cell pluripotency.