The CD47/TSP-1 axis: a promising avenue for ovarian cancer treatment and biomarker research.

Background: Ovarian cancer (OC) remains one of the most challenging and deadly malignancies facing women today. While PARP inhibitors (PARPis) have transformed the treatment landscape for women with advanced OC, many patients will relapse and the PARPi-resistant setting is an area of unmet medical need. Traditional immunotherapies targeting PD-1/PD-L1 have failed to show any benefit in OC.

LRP-1-dependent control of calpain expression and activity: A new mechanism regulating thyroid carcinoma cell adhesion.

The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP1 also regulates cell surface expression of matrix receptors by modulating both extracellular and intracellular signals, though current knowledge of the underlying mechanisms remains partial in the frame of cancer cells interaction with matricellular substrates. In this study we identified that LRP1 downregulates calpain activity and calpain 2 transcriptional expression in an invasive thyroid carcinoma cell model.

Contribution of the Low-Density Lipoprotein Receptor Family to Breast Cancer Progression.

The low-density lipoprotein receptor (LDLR) family comprises 14 single-transmembrane receptors sharing structural homology and common repeats. These receptors specifically recognize and internalize various extracellular ligands either alone or complexed with membrane-spanning co-receptors that are then sorted for lysosomal degradation or cell-surface recovery. As multifunctional endocytic receptors, some LDLR members from the core family were first considered as potential tumor suppressors due to their clearance activity against extracellular matrix-degrading enzymes.

Functional Interplay Between Collagen Network and Cell Behavior Within Tumor Microenvironment in Colorectal Cancer.

Colorectal cancer is the second most common cancer diagnosed in men and the third most commonly occurring in women worldwide. Interactions between cells and the surrounding extracellular matrix (ECM) are involved in tumor development and progression of many types of cancer. The organization of the ECM molecules provides not only physical scaffoldings and dynamic network into which cells are embedded but also allows the control of many cellular behaviors including proliferation, migration, differentiation, and survival leading to homeostasis and morphogenesis regulation.

Periostin Limits Tumor Response to VEGFA Inhibition.

Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy.

Publisher Correction: Vimentin knockout results in increased expression of sub-endothelial basement membrane components and carotid stiffness in mice.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Identification of LRP-1 as an endocytosis and recycling receptor for β1-integrin in thyroid cancer cells.

LRP-1 is a large endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP-1 was reported to control focal adhesion turnover to optimize the adhesion-deadhesion balance to support invasion. To better understand how LRP-1 coordinates cell-extracellular matrix interface, we explored its ability to regulate cell surface integrins in thyroid carcinomas.

Vimentin knockout results in increased expression of sub-endothelial basement membrane components and carotid stiffness in mice.

Intermediate filaments are involved in stress-related cell mechanical properties and in plasticity via the regulation of focal adhesions (FAs) and the actomyosin network. We investigated whether vimentin regulates endothelial cells (ECs) and vascular smooth muscle cells (SMCs) and thereby influences vasomotor tone and arterial stiffness. Vimentin knockout mice (Vim) exhibited increased expression of laminin, fibronectin, perlecan, collagen IV and VE-cadherin as well as von Willebrand factor deposition in the subendothelial basement membrane.

Tenascin-C Orchestrates Glioblastoma Angiogenesis by Modulation of Pro- and Anti-angiogenic Signaling.

High expression of the extracellular matrix component tenascin-C in the tumor microenvironment correlates with decreased patient survival. Tenascin-C promotes cancer progression and a disrupted tumor vasculature through an unclear mechanism. Here, we examine the angiomodulatory role of tenascin-C.

AngioMatrix, a signature of the tumor angiogenic switch-specific matrisome, correlates with poor prognosis for glioma and colorectal cancer patients.

Angiogenesis represents a rate-limiting step during tumor progression. Targeting angiogenesis is already applied in cancer treatment, yet limits of anti-angiogenic therapies have emerged, notably because tumors adapt and recur after treatment. Therefore, there is a strong need to better understand the molecular and cellular mechanisms underlying tumor angiogenesis.

Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model.

The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic β-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis.

LRP-1--CD44, a new cell surface complex regulating tumor cell adhesion.

The low-density lipoprotein receptor-related protein 1 (LRP-1) is a large endocytic receptor mediating the clearance of various molecules from the extracellular matrix. In the field of cancer, LRP-1-mediated endocytosis was first associated with antitumor properties. However, recent results suggested that LRP-1 may coordinate the adhesion-deadhesion balance in malignant cells to support tumor progression.

Advances in tenascin-C biology.

Tenascin-C is an extracellular matrix glycoprotein that is specifically and transiently expressed upon tissue injury. Upon tissue damage, tenascin-C plays a multitude of different roles that mediate both inflammatory and fibrotic processes to enable effective tissue repair. In the last decade, emerging evidence has demonstrated a vital role for tenascin-C in cardiac and arterial injury, tumor angiogenesis and metastasis, as well as in modulating stem cell behavior.

LRP-1 promotes cancer cell invasion by supporting ERK and inhibiting JNK signaling pathways.

Background: The low-density lipoprotein receptor-related protein-1 (LRP-1) is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated.

LRP-1: a new modulator of cytoskeleton dynamics and adhesive complex turnover in cancer cells.

The low-density lipoprotein receptor-related protein-1 (LRP-1)is a large scavenger receptor mediating the internalization and catabolism of various biological components from the extracellular matrix. In the past decade, LRP-1 appeared as an attractive receptor for targeting the invasive behavior of cancer cells since this protein is able to reduce the accumulation of extracellular proteinases by endocytosis. However, recent data suggest that LRP-1 could support carcinoma cell invasion depending on the cellular environment.

De novo ceramide synthesis is responsible for the anti-tumor properties of camptothecin and doxorubicin in follicular thyroid carcinoma.

Doxorubicin and camptothecin are two cytotoxic chemotherapeutic agents triggering apoptosis in various cancer cells, including thyroid carcinoma cells. Recent studies revealed a critical role of ceramide in chemotherapy and suggested that anti-cancer drugs may kill tumor cells through sphingomyelinase activation. However, in comparison to sphingomyelin hydrolysis, the relative involvement of de novo ceramide synthesis remained poorly explored and highly controversial.

Thrombospondin-1 enhances human thyroid carcinoma cell invasion through urokinase activity.

Previous studies reported that modification in the expression of the matricellular multidomain glycoprotein thrombospondin-1 (TSP-1) could play a critical role in the control of tumor progression and metastasis development. The function of this multimodular protein in cancers appears highly dependent on the cellular context and thus remains to date very difficult to accurately characterize. Controversial results indeed exist reporting either pro- or anti-invasive properties of TSP-1.

LRP-1 silencing prevents malignant cell invasion despite increased pericellular proteolytic activities.

The scavenger receptor low-density lipoprotein receptor-related protein 1 (LRP-1) mediates the clearance of a variety of biological molecules from the pericellular environment, including proteinases which degrade the extracellular matrix in cancer progression. However, its accurate functions remain poorly explored and highly controversial. Here we show that LRP-1 silencing by RNA interference results in a drastic inhibition of cell invasion despite a strong stimulation of pericellular matrix metalloproteinase 2 and urokinase-type plasminogen activator proteolytic activities.