Cancer resistance, high molecular weight hyaluronic acid, and longevity

Fisher, Gary J.

doi:10.1007/s12079-015-0278-6

Cited by 22 publications

(17 citation statements)

References 3 publications

(3 reference statements)

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“…Clinical analyses show that elevated HA accumulation in either the stroma or tumor parenchyma of many cancers is linked to tumor aggression and poor outcome (Sironen et al, 2011 ; McAtee et al, 2014 ; Chanmee et al, 2016 ; Sato et al, 2016 ; Turley et al, 2016 ; Bourguignon et al, 2017 ; Wu et al, 2017 ). Unexpectedly, HA has also recently been implicated as a stromal tumor-suppressing factor (Tian et al, 2013 ; Fisher, 2015 ; Triggs-Raine and Natowicz, 2015 ; Bohaumilitzky et al, 2017 ). These opposing effects are not well-understood but have been linked to differences in its metabolism and in particular the regulation of HA polymer size (Simpson and Lokeshwar, 2008 ; Tian et al, 2013 ; Khaldoyanidi et al, 2014 ; Tolg et al, 2014 ; Litwiniuk et al, 2016 ; Turley et al, 2016 ; Fouladi-Nashta et al, 2017 ).…”

Section: Stromal Hyaluronan Is Linked To Tumor Susceptibility and Cafmentioning

confidence: 99%

Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression

McCarthy¹,

El-Ashry²,

Turley

2018

Front. Cell Dev. Biol.

105

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This review summarizes the roles of CAFs in forming a “cancerized” fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA) in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM) and associated biomechanical changes in tumor stroma. Tumor stroma is often fibrotic and rich in fibrillar type I collagen and hyaluronan (HA). Cancer-associated fibroblasts (CAFs) are a major source of this fibrotic ECM. CAFs organize collagen fibrils and these biomechanical alterations provide highways for invading carcinoma cells either under the guidance of CAFs or following their epithelial to mesenchymal transition (EMT). The increased HA metabolism of a tumor microenvironment instructs carcinoma initiation and dissemination by performing multiple functions. The key effects of HA reviewed here are its role in activating CAFs in pre-malignant and malignant stroma, and facilitating invasion by promoting motility of both CAFs and tumor cells, thus facilitating their invasion. Circulating CAFs (cCAFs) also form heterotypic clusters with circulating tumor cells (CTC), which are considered to be pre-cursors of metastatic colonies. cCAFs are likely required for extravasation of tumors cells and to form a metastatic niche suitable for new tumor colony growth. Therapeutic interventions designed to target both HA and CAFs in order to limit tumor spread and increase response to current therapies are discussed.

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Section: Stromal Hyaluronan Is Linked To Tumor Susceptibility and Cafmentioning

confidence: 99%

Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression

McCarthy¹,

El-Ashry²,

Turley

2018

Front. Cell Dev. Biol.

105

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“…This extremely high-molecular-weight hyaluronan contributes to the exceptionally high longevity and unusual resistance to cancer displayed by naked mole rats. 71 – 76 The different HAS enzymes present a specific special-temporal distribution throughout development. 77 Interestingly, our work shows that all three HAS enzymes are expressed in the LSC niche and that all three are required to produce a transient HA matrix that supports cornea regeneration after injury.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation

Gesteira

Sun

Coulson-Thomas

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeLimbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function.MethodsHyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice—HAS1−/−;HAS3−/−, HAS2Δ/ΔCorEpi, TSG-6−/−—were used to determine the importance of the HA niche in LSC differentiation and specification.ResultsOur data demonstrate that the LSC niche is composed of a HA rich extracellular matrix. HAS1−/−;HAS3−/−, HAS2Δ/ΔCorEpi, and TSG-6−/− mice have delayed wound healing and increased inflammation after injury. Interestingly, upon insult the HAS knock-out mice up-regulate HA throughout the cornea through a compensatory mechanism, and in turn this alters LSC and epithelial cell specification.ConclusionsThe LSC niche is composed of a specialized HA matrix that differs from that present in the rest of the corneal epithelium, and the disruption of this specific HA matrix within the LSC niche leads to compromised corneal epithelial regeneration. Finally, our findings suggest that HA has a major role in maintaining the LSC phenotype.

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“…Resistance to cancer and extraordinary life span are hallmarks of the naked mole-rat [ 35 ]. Therefore, it was our aim to investigate the composition of the cultivable microbiota of these animals.…”

Section: Discussionmentioning

confidence: 99%

Analysis of cultivable microbiota and diet intake pattern of the long-lived naked mole-rat

et al. 2016

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BackgroundA variety of microbial communities exist throughout the human and animal body. Genetics, environmental factors and long-term dietary habit contribute to shaping the composition of the gut microbiota. For this reason the study of the gut microbiota of a mammal exhibiting an extraordinary life span is of great importance. The naked mole-rat (Heterocephalus glaber) is a eusocial mammal known for its longevity and cancer resistance.MethodsHere we analyzed its gut microbiota by cultivating the bacteria under aerobic and anaerobic conditions and identifying their species by mass spectrometry.ResultsAltogether, 29 species of microbes were identified, predominantly belonging to Firmicutes, and Bacteroidetes. The most frequent species were Bacillus megaterium (45.2 %), followed by Bacteroides thetaiotaomicron (19.4 %), Bacteroides ovatus, Staphylococcus sciuri and Paenibacillus spp., each with a frequency of 16.1 %.ConclusionOverall, the gut of the naked mole-rat is colonized by diverse, but low numbers of cultivable microbes compared with humans and mice. The primary food plants of the rodents are rich in polyphenols and related compounds, possessing anti-microbial, anti-inflammatory, anti-oxidative as well as anti-cancer activity which may contribute to their exceptionally healthy life.Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-016-0107-3) contains supplementary material, which is available to authorized users.

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Cancer resistance, high molecular weight hyaluronic acid, and longevity

Cited by 22 publications

References 3 publications

Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression

Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression

Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation

Analysis of cultivable microbiota and diet intake pattern of the long-lived naked mole-rat

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