Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer.

Abstract: Locoregional failure (LRF) in patients with breast cancer post-surgery and post-irradiation is linked to a dismal prognosis. In a refined new model, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1/CD203a (ENPP1) to be closely associated with LRF. ENPP1hi circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism.

An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer.

KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1.

The Usefulness of Bone Biomarkers for Monitoring Treatment Disease: A Comparative Study in Osteolytic and Osteosclerotic Bone Metastasis Models.

Background: The skeleton is the most common site of colonization by metastatic cancers. Zoledronic acid (ZA) has been shown to be effective for the treatment of bone metastases regardless of whether the bone lesions are osteolytic or osteoblastic. Biochemical markers of bone turnover may be useful tools to quantify the degree of bone remodeling in the presence of bone metastases.

EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth.

Background: Activated protein C/endothelial protein C receptor (APC/EPCR) axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated.

Matrix-Gla protein promotes osteosarcoma lung metastasis and associates with poor prognosis.

Osteosarcoma (OS) is the most prevalent osseous tumour in children and adolescents and, within this, lung metastases remain one of the factors associated with a dismal prognosis. At present, the genetic determinants driving pulmonary metastasis are poorly understood. We adopted a novel strategy using robust filtering analysis of transcriptomic profiling in tumour osteoblastic cell populations derived from human chemo-naive primary tumours displaying extreme phenotypes (indolent versus metastatic) to uncover predictors associated with metastasis and poor survival.

Sphere-derived tumor cells exhibit impaired metastasis by a host-mediated quiescent phenotype.

The spread of lung cancer cells to distant sites represents a common event associated with poor prognosis. A fraction of tumor cells named cancer stem cells (CSCs) have the ability to overcome therapeutic stress and remain quiescent. However, whether these CSCs have also the capacity to initiate and sustain metastasis remains unclear.

miRNA cargo within exosome-like vesicle transfer influences metastatic bone colonization.

Bone metastasis represents one of the most deleterious clinical consequences arising in the context of many solid tumors. Severe osteolysis results from tumor cell colonization of the bone compartment, a process which entails reciprocal exchange of soluble signals between tumor cells and their osseous microenvironment. Recent evidence indicates that tumor-intrinsic miRNAs are pleiotropic regulators of gene expression.

miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis.

Recent evidence suggests that miRNAs could be used as serum markers in a variety of normal and pathological conditions. In this study, we aimed to identify novel miRNAs associated with skeletal metastatic disease in a preclinical model of lung cancer bone metastasis. We assessed the validity of these miRNAs as reliable serum biochemical markers to monitor the extent of disease and response to treatment in comparison to imaging techniques and standard biochemical markers of bone turnover.

Receptor of activated protein C promotes metastasis and correlates with clinical outcome in lung adenocarcinoma.

Rationale: Efficient metastasis requires survival and adaptation of tumor cells to stringent conditions imposed by the extracellular milieu. Identification of critical survival signaling pathways in tumor cells might unveil novel targets relevant in disease progression.

Objectives: To investigate the contribution of activated protein C (APC) and its receptor (endothelial protein C receptor [EPCR]) in animal models of lung cancer metastasis and in patients with lung adenocarcinoma.

Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) reduces cell survival, homing, and colonization in lung cancer bone metastasis.

Purpose: We investigated the role of the collagen-binding receptor discoidin domain receptor-1 (DDR1) in the initiation and development of bone metastasis.

Experimental Design: We conducted immunohistochemical analyses in a cohort of 83 lung cancer specimens and examined phosphorylation status in a panel of human lung cancer cell lines. Adhesion, chemotaxis, invasiveness, metalloproteolytic, osteoclastogenic, and apoptotic assays were conducted in DDR1-silenced cells.

Tumor-stromal interactions of the bone microenvironment: in vitro findings and potential in vivo relevance in metastatic lung cancer models.

Lung cancer comprises a large variety of histological subtypes with a frequent proclivity to form bone metastasis; a condition associated with dismal prognosis. To identify common mechanisms in the development of osteolytic metastasis, we systematically screened a battery of lung cancer cell lines and developed three models of non-small cell lung cancer (NSCLC) with a common proclivity to form osseous lesions, which represented different histological subtypes. Comparative analysis revealed different incidences and latency times.