Untitled

Glinsky, Gennadi V.

doi:10.1023/a:1006050302406

Cited by 28 publications

(8 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Small peptides that directly target the biosynthesis of ECM proteins such as fibronectin have been developed [ 190 ]. When cancer cells adhere to certain ECM proteins it has been shown they acquire chemoresistance through activation of certain survival pathways [ 191 , 192 , 193 , 194 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Senthebane

Jonker

Rowe

et al. 2018

IJMS

111

176

View full text Add to dashboard Cite

Background: The functional interplay between tumor cells and their adjacent stroma has been suggested to play crucial roles in the initiation and progression of tumors and the effectiveness of chemotherapy. The extracellular matrix (ECM), a complex network of extracellular proteins, provides both physical and chemicals cues necessary for cell proliferation, survival, and migration. Understanding how ECM composition and biomechanical properties affect cancer progression and response to chemotherapeutic drugs is vital to the development of targeted treatments. Methods: 3D cell-derived-ECMs and esophageal cancer cell lines were used as a model to investigate the effect of ECM proteins on esophageal cancer cell lines response to chemotherapeutics. Immunohistochemical and qRT-PCR evaluation of ECM proteins and integrin gene expression was done on clinical esophageal squamous cell carcinoma biopsies. Esophageal cancer cell lines (WHCO1, WHCO5, WHCO6, KYSE180, KYSE 450 and KYSE 520) were cultured on decellularised ECMs (fibroblasts-derived ECM; cancer cell-derived ECM; combinatorial-ECM) and treated with 0.1% Dimethyl sulfoxide (DMSO), 4.2 µM cisplatin, 3.5 µM 5-fluorouracil and 2.5 µM epirubicin for 24 h. Cell proliferation, cell cycle progression, colony formation, apoptosis, migration and activation of signaling pathways were used as our study endpoints. Results: The expression of collagens, fibronectin and laminins was significantly increased in esophageal squamous cell carcinomas (ESCC) tumor samples compared to the corresponding normal tissue. Decellularised ECMs abrogated the effect of drugs on cancer cell cycling, proliferation and reduced drug induced apoptosis by 20–60% that of those plated on plastic. The mitogen-activated protein kinase-extracellular signal-regulated kinase (MEK-ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways were upregulated in the presence of the ECMs. Furthermore, our data show that concomitant addition of chemotherapeutic drugs and the use of collagen- and fibronectin-deficient ECMs through siRNA inhibition synergistically increased cancer cell sensitivity to drugs by 30–50%, and reduced colony formation and cancer cell migration. Conclusion: Our study shows that ECM proteins play a key role in the response of cancer cells to chemotherapy and suggest that targeting ECM proteins can be an effective therapeutic strategy against chemoresistant tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Senthebane

Jonker

Rowe

et al. 2018

IJMS

111

176

View full text Add to dashboard Cite

show abstract

“…Initiated by the primary adhesive interaction with the endothelium, homotypic aggregation of cancer cells could facilitate local microcirculatory aberrations and promote intravascular mechanical trapping. In addition, because enhanced homotypic aggregation of metastatic cancer cells has been shown to correlate with their ability to survive and resist apoptosis (18,19,27), the homotypic aggregates of endothelium-attached cancer cells may promote intravascular survival of metastatic cancer cells and serve as the seeds of early metastatic colonies. Consistent with this idea, recent experiments show that metastatic cancer cells exhibit increased resistance to circulatory stress-induced apoptosis in vivo in contrast to poorly metastatic cancer cells (28).…”

Section: Discussionmentioning

confidence: 99%

MDA-MB-435 Human Breast Carcinoma Cell Homo- and Heterotypic Adhesion under Flow Conditions Is Mediated in Part by Thomsen-Friedenreich Antigen-Galectin-3 Interactions

Khaldoyanidi¹,

Glinsky²,

Sikora³

et al. 2003

Journal of Biological Chemistry

Self Cite

196

162

View full text Add to dashboard Cite

Understanding cellular and molecular mechanisms of tumor metastasis is critically important for the development of new approaches to cancer treatment. One of the rate-limiting steps in metastatic dissemination is the adhesion of circulating cancer cells to the microvascular endothelium (for review, see Ref. 1). Recent experimental evidence identified endotheliumattached blood-born tumor cells as the seeds of secondary tumors (2). In the lung, early metastatic colonies were entirely within the blood vessels, and hematogenous metastases originated from the intravascular proliferation of tumor cells anchored to the endothelia (2). These results underscored the significance of intravascular intercellular adhesion in cancer metastasis.Although there is a substantial body of evidence demonstrating the role of various adhesion molecules in tumor cell adhesion (1, 3), the molecular and cellular mechanisms of cancer cell adhesion are still often modeled after the dynamics of the leukocyte adhesion cascade. Despite the many physical similarities, interaction of leukocytes and circulating malignant cells with the vascular endothelium are likely to be driven by distinct molecular mechanisms. For example, it is well documented that under conditions of shear force, circulating leukocytes participate in a multi-step cascade of sequential adhesion events involving rolling, adhesion, and transmigration across the vascular wall, where rolling is the first and rate-limiting step ultimately required for stable leukocyte adhesion to the endothelial cells (EC) 1 (4). However, in contrast to leukocytes, published data regarding the rolling and adhesion of tumor cells on vascular endothelium suggest a non-leukocyte-like mechanism (5-9). Furthermore, it is also not clear whether this step is required for stable adhesion of tumor cells to the endothelium. Leukocyte rolling is mostly mediated by the interaction of the members of C-type lectin family, selectins, with their cognate carbohydrate ligands (4, 10). Studies from our laboratories (11, 12) as well as other investigators (13) have recently shown that another lectin, galectin-3, plays a key role in initiating the adhesion of human breast and prostate cancer cells to the endothelium by specifically interacting with the cancerassociated carbohydrate, T antigen. However, these studies were carried out under static conditions, and the relevance of galectin-3-T antigen interactions in mediating cancer cell adhesion under conditions of flow has not been investigated.Shear forces have an important influence on cell adhesion and other cellular functions, and malignant cell lines appear to possess different adhesive properties under static and dynamic conditions (14,15). To elucidate the molecular mechanisms of intercellular adhesive interactions relevant to breast cancer metastasis, we examined the adhesive behavior of two human breast carcinoma cell lines exhibiting distinct metastatic po-

show abstract

“…There is evidence that this glycocalyx is critically involved in cell‐adhesion and cell‐recognition processes. Nowadays, the important role of carbohydrates in a broad spectrum of physiological and pathological processes, including metastasis,1, 2 inflammation,3 and infection,4 is well established. All these processes imply a protein–carbohydrate interaction, but there is now clear evidence that carbohydrate–carbohydrate interactions between glycosphingolipid (GSL) clusters are also involved in these processes 5, 6.…”

Section: Introductionmentioning

confidence: 99%

Gold Glyconanoparticles as New Tools in Antiadhesive Therapy

et al. 2004

View full text Add to dashboard Cite

Gold glyconanoparticles (GNPs) have been prepared as new multivalent tools that mimic glycosphingolipids on the cell surface. GNPs are highly soluble under physiological conditions, stable against enzymatic degradation and nontoxic. Thereby GNPs open up a novel promising multivalent platform for biological applications. It has recently been demonstrated that specific tumor-associated carbohydrate antigens (glycosphingolipids and glycoproteins) are involved in the initial step of tumor spreading. A mouse melanoma model was selected to test glyconanoparticles as possible inhibitors of experimental lung metastasis. A carbohydrate-carbohydrate interaction is proposed as the first recognition step for this process. Glyconanoparticles presenting lactose (lacto-GNPs) have been used successfully to significantly reduce the progression of experimental metastasis. This result shows for the first time a clear biological effect of lacto-GNPs, demonstrating the potential application of this glyconanotechnology in biological processes.

show abstract

Untitled

Cited by 28 publications

References 36 publications

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

MDA-MB-435 Human Breast Carcinoma Cell Homo- and Heterotypic Adhesion under Flow Conditions Is Mediated in Part by Thomsen-Friedenreich Antigen-Galectin-3 Interactions

Gold Glyconanoparticles as New Tools in Antiadhesive Therapy

Contact Info

Product

Resources

About