Heparanase Promotes Syndecan-1 Expression to Mediate Fibrillar Collagen and Mammographic Density in Human Breast Tissue Cultured ex vivo

Huang, Xuan; Reye, Gina; Momot, Konstantin I.; Blick, Tony; Lloyd, Thomas; Tilley, Wayne D.; Hickey, Theresa E.; Snell, Cameron; Okolicsanyi, Rachel K.; Haupt, Larisa M.; Ferro, Vito; Thompson, Erik W.; Hugo, Honor J.

doi:10.3389/fcell.2020.00599

Cited by 17 publications

(21 citation statements)

References 69 publications

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“…Cervical cancer, as one of the common human tumors, is one of the most common gynecological malignancies, [1][2][3][4][5]34 which is like other tumors [35][36][37][38][39][40][41] and they threatened seriously to human health as well as cervical cancer, [42][43][44][45][46][47][48] its morbidity and mortality rate are at the forefront of female malignancies. Surgery, radiotherapy and chemotherapy for early cervical cancer have good effects, but in advanced stage, the therapeutic effect of metastatic and recurrent cervical cancer is very limited and the survival rate is low.…”

Section: Discussionmentioning

confidence: 99%

<p>Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer</p>

Shi¹,

Wang²,

Dai³

et al. 2020

OTT

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Background Previous reports showed that APOC1 was associated with several cancers but the function of APOC1 in cervical cancer was unknown. This study aimed to investigate the clinical effect and function of APOC1 in cervical cancer. Materials and Methods In this study, the relative expression of APOC1 in cervical cancer was detected by RT-qPCR. In order to determine the cell proliferation and migration and invading ability and apoptosis more accurately, we used CCK8 assay, Edu assay, wound healing assay, migration and invasion assay, flow cytometry assay, co-immunoprecipitation, proteomics and Western blot by silencing and overexpressing APOC1 , respectively. The role of APOC1 on tumor progression was explored in vitro and vivo. Results The relative expression of APOC1 in cervical cancer tissues was up-regulated (P<0.05). In cervical cancer cell lines, silencing of APOC1 restrained cell progression and EMT, while over-expression of APOC1 accelerated cell progression and EMT in vivo and vitro (P<0.05). Conclusion APOC1 acts as an oncogene in cervical cancers and knockdown of APOC1 inhibited cervical cancer cells growth in vitro and in vivo. There is a close relationship between the relative expression of APOC1 and clinical outcome in cervical cancer patients.

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Section: Discussionmentioning

confidence: 99%

<p>Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer</p>

Shi¹,

Wang²,

Dai³

et al. 2020

OTT

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“…Melanoma progression [169] Inhibiting heparanase with either PG545 or PI-88 in patient-derived explants of normal mammary tissue increased MMP-2 mRNA expression Tissue density and breast cancer [192] siRNA knockdown of heparanase in SUM149 breast cancer cells reduced MMP-2 mRNA expression…”

Section: Treatment Of Cells With Heparanase Inhibitor Sst0001 Suppressed Inos Expressionmentioning

confidence: 99%

The Heparanase Regulatory Network in Health and Disease

Mayfosh

Nguyen

Hulett

2021

IJMS

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The extracellular matrix (ECM) is a structural framework that has many important physiological functions which include maintaining tissue structure and integrity, serving as a barrier to invading pathogens, and acting as a reservoir for bioactive molecules. This cellular scaffold is made up of various types of macromolecules including heparan sulfate proteoglycans (HSPGs). HSPGs comprise a protein core linked to the complex glycosaminoglycan heparan sulfate (HS), the remodeling of which is important for many physiological processes such as wound healing as well as pathological processes including cancer metastasis. Turnover of HS is tightly regulated by a single enzyme capable of cleaving HS side chains: heparanase. Heparanase upregulation has been identified in many inflammatory diseases including atherosclerosis, fibrosis, and cancer, where it has been shown to play multiple roles in processes such as epithelial-mesenchymal transition, angiogenesis, and cancer metastasis. Heparanase expression and activity are tightly regulated. Understanding the regulation of heparanase and its downstream targets is attractive for the development of treatments for these diseases. This review provides a comprehensive overview of the regulators of heparanase as well as the enzyme’s downstream gene and protein targets, and implications for the development of new therapeutic strategies.

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“…The accumulation of collagen alone promotes breast cancer in mice [7], and the arrangement of collagens (typical of those seen in HMD) has been associated with poor survival in BC patients [8]. We have shown that collagen alignment is instrumental in maintaining MD in human breast tissue cultured ex vivo [9]. Furthermore, MD has been implicated in creating an environment of increased stiffness, which in turn may be a contributing factor to MD-associated breast cancer risk [10].…”

Section: Introductionmentioning

confidence: 86%

“…Ltd., Macquarie Park, NSW, Australia). cDNA was synthesized and QPCR performed as previously described [9] using primer sequences shown in Table 2.…”

Section: Quantitative Real-time Polymerase Chain Reaction (Qpcr)mentioning

confidence: 99%

“…For controls, serial sections were treated the same as for test sections, except that the primary antibody was omitted. Abundance of collagen I as a means to determine mammary tissue stiffness has been used by others and by us [3,9]. Similarly, we stained mammary tissues with picrosirius red and viewed them under polarized light, and used ImageJ to delineate the image into the red and green channels.…”

Section: Embedding and Immunohistochemistry (Ihc)mentioning

confidence: 99%

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RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers

Reye

Huang

Britt

et al. 2021

Cancers

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High mammographic density (MD) increases breast cancer (BC) risk and creates a stiff tissue environment. BC risk is also increased in BRCA1/2 gene mutation carriers, which may be in part due to genetic disruption of the tumour suppressor gene Ras association domain family member 1 (RASSF1A), a gene that is also directly regulated by tissue stiffness. High MD combined with BRCA1/2 mutations further increase breast cancer risk, yet BRCA1/2 mutations alone or in combination do not increase MD. The molecular basis for this additive effect therefore remains unclear. We studied the interplay between MD, stiffness, and BRCA1/2 mutation status in human mammary tissue obtained after prophylactic mastectomy from women at risk of developing BC. Our results demonstrate that RASSF1A expression increased in MCF10DCIS.com cell cultures with matrix stiffness up until ranges corresponding with BiRADs 4 stiffnesses (~16 kPa), but decreased in higher stiffnesses approaching malignancy levels (>50 kPa). Similarly, higher RASSF1A protein was seen in these cells when co-cultivated with high MD tissue in murine biochambers. Conversely, local stiffness, as measured by collagen I versus III abundance, repressed RASSF1A protein expression in BRCA1, but not BRCA2 gene mutated tissues; regional density as measured radiographically repressed RASSF1A in both BRCA1/2 mutated tissues. The combinatory effect of high MD and BRCA mutations on breast cancer risk may be due to RASSF1A gene repression in regions of increased tissue stiffness.

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Heparanase Promotes Syndecan-1 Expression to Mediate Fibrillar Collagen and Mammographic Density in Human Breast Tissue Cultured ex vivo

Cited by 17 publications

References 69 publications

<p>Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer</p>

<p>Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer</p>

The Heparanase Regulatory Network in Health and Disease

RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers

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