Hyaluronan in the Healthy and Malignant Hematopoietic Microenvironment

Khaldoyanidi, Sophia; Goncharova, Valentina; Mueller, Barbara M.; Schraufstätter, Ingrid U.

doi:10.1016/b978-0-12-800092-2.00006-x

Cited by 26 publications

(20 citation statements)

References 192 publications

(173 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Membrane-bound or free extracellular HA favors tumor progression by inducing tumor cell motility, invasive properties, proliferation, production of growth factors and epithelial-mesenchymal transition [105]. HA is also involved in the regulation, proliferation and differentiation of hematopoietic cells in bone marrow [109].…”

Section: Tumor-produced Hyaluronanmentioning

confidence: 99%

Mechanisms of immune evasion in bladder cancer

Crispen

Kusmartsev

2019

Cancer Immunol Immunother

142

117

View full text Add to dashboard Cite

With the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway). While these trials have demonstrated promising results and improvements over existing therapies, less than half of patients with advanced disease demonstrate clinical benefit from checkpoint inhibitor therapy. Recent breakthroughs in cancer biology and immunology have led to an improved understanding of the influence of the tumor microenvironment on the host's immune system. It appears that tumors promote the formation of highly immunosuppressive microenvironments preventing generation of effective anti-tumor immune response through multiple mechanisms. Therefore, reconditioning of the tumor microenvironment and restoration of the competent immune response is essential for achieving optimal efficacy of cancer immunotherapy. In this review, we aim to discuss the major mechanisms of immune evasion in bladder cancer and highlight novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes.

show abstract

Section: Tumor-produced Hyaluronanmentioning

confidence: 99%

Mechanisms of immune evasion in bladder cancer

Crispen

Kusmartsev

2019

Cancer Immunol Immunother

142

117

View full text Add to dashboard Cite

show abstract

“…Under normal homeostatic conditions HA metabolism is carefully controlled to maintain physiological concentration in tissues. Furthermore, changes in HA synthesis and/or degradation are hallmarks of an ongoing pathological process ( 32 ). The three mammalian HAS enzymes (HAS1–3) synthesize and secrete HA polymers of different length; HA secreted into the culture media by stable transfectants revealed that HAS1 makes MMW-to-HMW-HA (200-2000 kDa), whereas HAS2 is responsible for only HMW polymers (>2000 kDa).…”

Section: Physiologic and Pathophysiologic Mechanisms Of Ha Mw Modificmentioning

confidence: 99%

Hyaluronan â€“ A Functional and Structural Sweet Spot in the Tissue Microenvironment

2015

View full text Add to dashboard Cite

Transition from homeostatic to reactive matrix remodeling is a fundamental adaptive tissue response to injury, inflammatory disease, fibrosis, and cancer. Alterations in architecture, physical properties, and matrix composition result in changes in biomechanical and biochemical cellular signaling. The dynamics of pericellular and extracellular matrices, including matrix protein, proteoglycan, and glycosaminoglycan modification are continually emerging as essential regulatory mechanisms underlying cellular and tissue function. Nevertheless, the impact of matrix organization on inflammation and immunity in particular and the consequent effects on tissue healing and disease outcome are arguably under-studied aspects of adaptive stress responses. Herein, we review how the predominant glycosaminoglycan hyaluronan (HA) contributes to the structure and function of the tissue microenvironment. Specifically, we examine the evidence of HA degradation and the generation of biologically active smaller HA fragments in pathological settings in vivo. We discuss how HA fragments versus nascent HA via alternate receptor-mediated signaling influence inflammatory cell recruitment and differentiation, resident cell activation, as well as tumor growth, survival, and metastasis. Finally, we discuss how HA fragmentation impacts restoration of normal tissue function and pathological outcomes in disease.

show abstract

“…CD44 is required for LSCs to efficiently lodge in and home to the BM niche in AML, and anti-CD44 antibodies may modify the fate of the LSCs via inducing differentiation (6). In addition, CD44-HA crosstalk mediates LSC apoptosis resistance by initiating signal transductions and cooperating with multidrug resistance genes (17). The results of the present study demonstrated that CD44 expression of BM-MSCs was significantly increased after LSC simulation.…”

Section: Discussionmentioning

confidence: 54%

Leukemia stem cells promote chemoresistance by inducing downregulation of lumican in mesenchymal stem cells

et al. 2019

View full text Add to dashboard Cite

Leukemia stem cells (LSCs) are responsible for therapeutic failure and relapse of acute lymphoblastic leukemia. As a result of the interplay between LSCs and bone marrow mesenchymal stem cells (BM-MSCs), cancer cells may escape from chemotherapy and immune surveillance, thereby promoting leukemia progress and relapse. The present study identified that the crosstalk between LSCs and BM-MSCs may contribute to changes of immune phenotypes and expression of hematopoietic factors in BM-MSCs. Furthermore, Illumina Genome Analyzer/Hiseq 2000 identified 7 differentially expressed genes between BM-MSCs LSC and BM-MSCs. The Illumina sequencing results were further validated by reverse transcription-quantitative polymerase chain reaction. Following LSC simulation, 2 genes were significantly upregulated, whereas the remaining 2 genes were significantly downregulated in MSCs. The most remarkable changes were identified in the expression levels of lumican (LUM) gene. These results were confirmed by western blot analysis. In addition, decreased LUM expression led to decreased apoptosis, and promoted chemoresistance to VP-16 in Nalm-6 cells. These results suggest that downregulation of LUM expression in BM-MSCs contribute to the anti-apoptotic properties and resistance to chemotherapy in LSCs.

show abstract

Hyaluronan in the Healthy and Malignant Hematopoietic Microenvironment

Cited by 26 publications

References 192 publications

Mechanisms of immune evasion in bladder cancer

Mechanisms of immune evasion in bladder cancer

Hyaluronan â€“ A Functional and Structural Sweet Spot in the Tissue Microenvironment

Leukemia stem cells promote chemoresistance by inducing downregulation of lumican in mesenchymal stem cells

Contact Info

Product

Resources

About