Hyaluronan, Inflammation, and Breast Cancer Progression

Schwertfeger, Kathryn L.; Cowman, Mary K.; Telmer, Patrick G.; Turley, Eva A.; McCarthy, James B.

doi:10.3389/fimmu.2015.00236

Cited by 176 publications

(146 citation statements)

References 130 publications

(192 reference statements)

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“…Evidence is emerging that specific size ranges of HA fragments exert differential effects on tumor cell migration and growth [4, 22]. In addition, HA fragmentation within ectopic sites promotes the influx of host pro-tumorigenic macrophages and activate endothelial cells to stimulate angiogenesis [2]. Thus, aggressive immigrant tumor cells that have developed the ability to autonomously synthesize HA, assemble it into pericellular matrices and fragment/process the HA polymers have a selective advantage in metastasis.…”

Section: Ha Pericellular Matrices Fragments and Metastasismentioning

confidence: 99%

Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment

2016

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Hyaluronan (HA) is a structurally simple polysaccharide, but its ability to act as a template for organizing pericellular matrices and its regulated synthesis and degradation are key to initiating repair responses. Importantly, these HA functions are usurped by tumor cells to facilitate progression and metastasis. Recent advances have identified the functional complexities associated with the synthesis and degradation of HA rich matrices. Three enzymes synthesize large HA polymers while multiple hyaluronidases or tissue free radicals degrade these into smaller bioactive fragments. A family of extracellular and cell associated HA binding proteins/receptors translate the bioinformation encrypted in this complex polymer mixture to activate signaling networks required for cell survival, proliferation and migration in an actively remodeling microenvironment. Changes in HA metabolism within both the peritumor stroma and parenchyma are linked to tumor initiation, progression and poor clinical outcome. We review evidence that metastatic tumor cells must acquire the capability to autonomously synthesize, assemble and process their own ‘portable’ HA rich microenvironments in order to survive in the circulation, metastasize to ectopic sites and escape therapeutic intervention. Strategies to disrupt the HA machinery of primary tumor and circulating tumor cells may enhance the effectiveness of current conventional and targeted therapies.

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Section: Ha Pericellular Matrices Fragments and Metastasismentioning

confidence: 99%

Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment

2016

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“…There are many excellent reviews on the roles of HA in different fields, such as in angiogenesis [4], reactive oxygen species [13], HA digestion [14], cancer [3, 15, 16], cancer therapeutics [17], cancer metastasis [18], chondrocytes [19], lung injury [20–22], wound healing [23], diabetes [24], leukocyte trafficking [25], and in immune regulation [5, 26, 27]. The current review will summarize the role of HA in biological and pathological conditions, and will emphasize the role of HA in human diseases.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan as a therapeutic target in human diseases

Liang

Jiang

Noble

2016

Advanced Drug Delivery Reviews

168

110

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Accumulation and turnover of extracellular matrix is a hallmark of tissue injury, repair and remodeling in human diseases. Hyaluronan is a major component of the extracellular matrix and plays an important role in regulating tissue injury and repair, and controlling disease outcomes. The function of hyaluronan depends on its size, location, and interactions with binding partners. While fragmented hyaluronan stimulates the expression of an array of genes by a variety of cell types regulating inflammatory responses and tissue repair, cell surface hyaluronan provides protection against tissue damage from the environment and promotes regeneration and repair. The interactions of hyaluronan and its binding proteins participate in the pathogenesis of many human diseases. Thus, targeting hyaluronan and its interactions with cells and proteins may provide new approaches to developing therapeutics for inflammatory and fibrosing diseases. This review focuses on the role of hyaluronan in biological and pathological processes, and as a potential therapeutic target in human diseases.

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“…Cancer cells promote a transition from homeostatic to a reactive, inflammatory remodeled surrounding extracellular matrix, including hyaluronan where hyaluronan fragments appear to be biologically active, of pro-inflammatory nature, activating signal pathways that promote survival of tumor cells, their migration and invasiveness [50,51]. Hyaluronan is, however, highly dependent on the presence of CD44 in the cells, particularly in cancer stem cells, that survive immune attacks [52,53].…”

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confidence: 99%

The ubiquitous hyaluronan: Functionally implicated in the oviduct?

et al. 2016

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Hyaluronan (hyaluronic acid) is a simple, non-antigenic, non-sulphated glycosaminoglycan (GAG) present everywhere in the extracellular compartments of the body. Noteworthy, it is highly conserved phylogenetically, from sauropsida to mammals; and plays a plethora of roles from embryonic/fetal development to adult physiological and pathological events, including tumor development. In reproduction, hyaluronan has proven related to initial events as sperm survival, build-up of the sperm reservoir in the oviduct, regulation of sperm capacitation and pre-fertilization to later participate in embryo, fetal and placental development. Synthesis, binding (via the CD44 membrane receptor) and degradation of hyaluronan occur in male and female genital organs, the oviduct being no exception. This review discusses our current knowledge on roles of this ubiquitous GAG on the survival of immunologically foreign spermatozoa in the pig oviduct, a relevant event for fertility. During pre-ovulatory storage in the functional tubal sperm reservoir, spermatozoa are entrapped in a mucus-like tubal fluid.This fluid contains fluctuating levels of hyaluronan, which is synthesized by the lining 18th ICAR-2016-S2. Pig reproduction Symp 2 epithelium by HA-synthase 3 (has3). Both hyaluronan and its CD44-receptor are particularly evident in the deep mucosal furrows of the sperm reservoir, where most spermatozoa are embedded in; kept alive, un-capacitated but also undetected by the immune system of the female. Hyaluronan is also present in the seminal plasma, and evidence points out an involvement of hyaluronan and its receptor in the local (tubal and possibly uterine) production of anti-inflammatory cytokines, such as IL-10, pertaining maternal immune tolerance of these foreign cells.

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Hyaluronan, Inflammation, and Breast Cancer Progression

Cited by 176 publications

References 130 publications

Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment

Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment

Hyaluronan as a therapeutic target in human diseases

The ubiquitous hyaluronan: Functionally implicated in the oviduct?

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