Emerging Roles for Hyaluronidase in Cancer Metastasis and Therapy

McAtee, Caitlin O.; Barycki, Joseph J.; Simpson, Melanie A.

doi:10.1016/b978-0-12-800092-2.00001-0

Cited by 163 publications

(145 citation statements)

References 118 publications

(171 reference statements)

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“…iRGD may also change the role of hyperthermia in IPC if it helps achieve a similar or higher degree of drug penetration than hyperthermia, or if iRGD and hyperthermia have additive/synergistic effects on intratumoral drug penetration. Importantly, iRGD does not appear to facilitate further peritoneal metastasis unlike some of the enzymatic drug delivery approaches that dissociate tumors (41, 42). In fact, iRGD may even be protective against peritoneal metastasis since it suppresses tumor cell motility as a chemorepellent (43).…”

Section: Discussionmentioning

confidence: 97%

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis

Sugahara

Scodeller

Braun

et al. 2015

Journal of Controlled Release

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Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy (IPC) is an area of intense interest given its efficacy in ovarian cancer. However, IPC suffers from poor drug penetration into peritoneal tumors. As such, extensive cytoreductive surgery is required prior to IPC. Here, we explore the utility of iRGD, a tumor-penetrating peptide, for improved tumor-specific penetration of intraperitoneal compounds and enhanced IPC in mice. Intraperitoneally administered iRGD significantly enhanced penetration of an attached fluorescein into disseminated peritoneal tumor nodules. The penetration was tumor-specific, circulation-independent, and mediated by the neuropilin-binding RXXK tissue-penetration peptide motif of iRGD. Q-iRGD, which fluoresces upon cleavage, including the one that leads to RXXK activation, specifically labeled peritoneal metastases displaying different growth patterns in mice. Importantly, iRGD enhanced intratumoral entry of intraperitoneally co-injected dextran to approximately 300% and doxorubicin to 250%. Intraperitoneal iRGD/doxorubicin combination therapy inhibited the growth of bulky peritoneal tumors and reduced systemic drug toxicity. iRGD delivered attached fluorescein and co-applied nanoparticles deep into fresh human peritoneal metastasis explants. These results indicate that intraperitoneal iRGD co-administration serves as a simple and effective strategy to facilitate tumor detection and improve the therapeutic index of IPC for peritoneal carcinomatosis.

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Section: Discussionmentioning

confidence: 97%

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis

Sugahara

Scodeller

Braun

et al. 2015

Journal of Controlled Release

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“…There are many excellent reviews on the topic [3, 15–18, 249]. An example of the role of HA in cancer can be seen in a recent report on naked mole rats.…”

Section: Hyaluronan In Human Diseasesmentioning

confidence: 99%

Hyaluronan as a therapeutic target in human diseases

Liang

Jiang

Noble

2016

Advanced Drug Delivery Reviews

178

117

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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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“…Hyal 1, 2 or 3). It can also be chemically cleaved by oxygen and nitrogen free radicals that are elevated in tumor microenvironments [19–21]. This two-pronged attack on HA polymers results in a complex mixture of oligosaccharides and larger fragments with a broad range in sizes (e.g.…”

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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Emerging Roles for Hyaluronidase in Cancer Metastasis and Therapy

Cited by 163 publications

References 118 publications

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis

Hyaluronan as a therapeutic target in human diseases

Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment

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