Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

Metastatic disease is the primary cause of death for most cancer patients. Complex and redundant pathways involving the tumor cell and the microenvironment mediate tumor invasion at the primary site, survival and arrest in the bloodstream, and progressive outgrowth at a distant site. Understanding these pathways and their dynamic interactions will help identify promising molecular targets for cancer therapy and key obstacles to their clinical development.

Tumor metastasis: mechanistic insights and clinical challenges

Despite recent progress in understanding the cancer genome, there is still a relative delay in understanding the full aspects of the glycome and glycoproteome of cancer. Glycobiology has been instrumental in relevant discoveries in various biological and medical fields, and has contributed to the deciphering of several human diseases. Glycans are involved in fundamental molecular and cell biology processes occurring in cancer, such as cell signalling and communication, tumour cell dissociation and invasion, cell-matrix interactions, tumour angiogenesis, immune modulation and metastasis formation. The roles of glycans in cancer have been highlighted by the fact that alterations in glycosylation regulate the development and progression of cancer, serving as important biomarkers and providing a set of specific targets for therapeutic intervention. This Review discusses the role of glycans in fundamental mechanisms controlling cancer development and progression, and their applications in oncology.

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Glycosylation in cancer: mechanisms and clinical implications

Mucins — large extracellular proteins that are heavily glycosylated with complex oligosaccharides — establish a selective molecular barrier at the epithelial surface and engage in morphogenetic signal transduction. Alterations in mucin expression or glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion and immune surveillance. Mucins are used as diagnostic markers in cancer, and are under investigation as therapeutic targets for cancer.

Mucins in cancer: Protection and control of the cell surface

Changes in glycosylation are often a hallmark of disease states. For example, cancer cells frequently display glycans at different levels or with fundamentally different structures than those observed on normal cells. This phenomenon was first described in the early 1970s, but the molecular details underlying such transformations were poorly understood. In the past decade advances in genomics, proteomics and mass spectrometry have enabled the association of specific glycan structures with disease states. In some cases, the functional significance of disease-associated changes in glycosylation has been revealed. This review highlights changes in glycosylation associated with cancer and chronic inflammation and new therapeutic and diagnostic strategies that are based on the underlying glycobiology.

Glycans in cancer and inflammation — potential for therapeutics and diagnostics

No abstract Abbreviations:Sia, sialic acid, type unspecified; Tn antigen, GalNAcα 1-O-Ser/Thr; T antigen, Galβ1-3GalNAcα-O-Ser/Thr; Sialyl LewisX, Siaα2-3Galβ1-4(Fucα1-3)GlcNAc; Sialyl Lewisa, Siaα2-3Galβ1-3(Fucα1-4)GlcNAc; Sialyl-Tn antigen, Siaα2-6GalNAcα1-O-Ser/Thr; FucT, fucosyltransferase; ST, sialyltransferase.

Perspectives on the significance of altered glycosylation of glycoproteins in cancer

Selectins are adhesion receptors that normally recognize certain vascular mucin-type glycoproteins bearing the carbohydrate structure sialyl-Lewisx. The clinical prognosis and metastatic progression of many epithelial carcinomas has been correlated independently with production of tumor mucins and with enhanced expression of sialyl-Lewisx. Metastasis is thought to involve the formation of tumor-platelet-leukocyte emboli and their interactions with the endothelium of distant organs. We provide a link between these observations by showing that P-selectin, which normally binds leukocyte ligands, can promote tumor growth and facilitate the metastatic seeding of a mucin-producing carcinoma. P-selectin-deficient mice showed significantly slower growth of subcutaneously implanted human colon carcinoma cells and generated fewer lung metastases from intravenously injected cells. Three potential pathophysiological mechanisms are demonstrated: first, intravenously injected tumor cells home to the lungs of P-selectin deficient mice at a lower rate; second, P-selectin-deficient mouse platelets fail to adhere to tumor cell-surface mucins; and third, tumor cells lodged in lung vasculature after intravenous injection often are decorated with platelet clumps, and these are markedly diminished in P-selectin-deficient animals.

https://www.pnas.org/content/pnas/95/16/9325.full.pdf

P-selectin deficiency attenuates tumor growth and metastasis.

Electrochemical capacitors and lithium-ion batteries have seen little change in their electrolyte chemistry since their commercialization, which has limited improvements in device performance. Combining superior physical and chemical properties and a high dielectric-fluidity factor, the use of electrolytes based on solvent systems that exclusively use components that are typically gaseous under standard conditions show a wide potential window of stability and excellent performance over an extended temperature range. Electrochemical capacitors using difluoromethane show outstanding performance from -78° to +65°C, with an increased operation voltage. The use of fluoromethane shows a high coulombic efficiency of ~97% for cycling lithium metal anodes, together with good cyclability of a 4-volt lithium cobalt oxide cathode and operation as low as -60°C, with excellent capacity retention.

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Liquefied gas electrolytes for electrochemical energy storage devices.

Selectins are adhesion molecules that mediate calcium-dependent cell-cell interactions among leukocytes, platelets, and endothelial cells. The naturally occurring vascular ligands for the selectins are mostly mucin-type glycoproteins. Increased expression and altered glycosylation of mucins are known to be prominent features of carcinoma progression. We have previously shown that all three selectins bind to colon carcinoma cell lines in a calcium-dependent fashion and that carcinoma growth and metastasis formation are attenuated in P-selectin-deficient mice. Here we show that the three recombinant soluble selectins recognize ligands within primary colon carcinoma tissue samples. Affinity chromatography showed that the ligands for all three selectins are O-sialoglycoprotease-sensitive mucins that are recognized in a calcium- and sialic acid-dependent manner. Furthermore, there are separate binding sites on the mucins for each selectin, allowing cross-binding of a single mucin molecule by more than one selectin. We also show that the selectin ligands on purified carcinoma mucins can mediate at least four different pathological interactions among platelets, leukocytes, and endothelial cells. These findings could explain some of the adhesive events of blood-borne tumor cells reported to occur with leukocytes, platelets, and endothelial cells, which are believed to play a part in modulating some early events in tumor metastases.

/pdf/distinct-selectin-ligands-on-colon-carcinoma-mucins-can-23g5d7jtc6.pdf

Distinct Selectin Ligands on Colon Carcinoma Mucins Can Mediate Pathological Interactions among Platelets, Leukocytes, and Endothelium

Highly sensitive hydrogen detection at room temperature can be realized by employing solution-processed MoS2 nanosheet-Pd nanoparticle composite. A MoS2-Pd composite exhibits greater sensing performance than its graphene counterpart, indicating that solvent exfoliated MoS2 holds great promise for inexpensive and scalable fabrication of highly sensitive chemical sensors.

/pdf/mos2-nanosheet-pd-nanoparticle-composite-for-highly-4xe50gzm5t.pdf

Young Jin Kim

Papers

Perspectives on the significance of altered glycosylation of glycoproteins in cancer

P-selectin deficiency attenuates tumor growth and metastasis.

Liquefied gas electrolytes for electrochemical energy storage devices.

Distinct Selectin Ligands on Colon Carcinoma Mucins Can Mediate Pathological Interactions among Platelets, Leukocytes, and Endothelium

MoS2 Nanosheet–Pd Nanoparticle Composite for Highly Sensitive Room Temperature Detection of Hydrogen