Enzymatic remodeling of heparan sulfate proteoglycans within the tumor microenvironment: Growth regulation and the prospect of new cancer therapies

Sanderson, Ralph D.; Yang, Yang; Kelly, Thomas J.; MacLeod, Veronica; Dai, Yuemeng; Theus, Allison

doi:10.1002/jcb.20602

Cited by 140 publications

(114 citation statements)

References 58 publications

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“…19 Heparanase (HPSE), an extracellular enzyme involved in this shedding, has been shown to be overexpressed in several tumours, increasing the metastatic potential. HPSE regulates both the level and localisation of syndecan-1 within the tumour microenvironment by inducing its shedding from the tumour cell surface and its de novo synthesis.…”

Section: Discussionmentioning

confidence: 99%

Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer

Ledezma¹,

Cifuentes²,

M³

et al. 2011

Asian J Androl

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The clinical features of prostate cancer do not provide an accurate determination of patients undergoing biochemical relapse and are therefore not suitable as indicators of prognosis for recurrence. New molecular markers are needed for proper pre-treatment risk stratification of patients. Our aim was to assess the value of altered expression of syndecan-1 and -2 as a marker for predicting biochemical relapse in patients with clinically localized prostate cancer treated by radical prostatectomy. The expression of syndecan-1 and -2 was examined by immunohistochemical staining in a series of 60 paraffin-embedded tissue samples from patients with localized prostate cancer. Ten specimens from patients with benign prostatic hyperplasia were used as non-malignant controls. Semiquantitative analysis was performed to evaluate the staining patterns. To investigate the prognostic value, Kaplan-Meier survival curves were performed and compared by a log-rank test. In benign samples, syndecan-1 was expressed in basal and secretory epithelial cells with basolateral membrane localisation, whereas syndecan-2 was expressed preferentially in basal cells. In prostate cancer samples, the expression patterns of both syndecans shifted to granular-cytoplasmic localisation. Survival analysis showed a significant difference (P,0.05) between normal and altered expression of syndecan-1 and -2 in free prostate-specific antigen recurrence survival curves. These data suggest that the expression of syndecan-1 and -2 can be used as a prognostic marker for patients with clinically localized prostate cancer, improving the prostate-specific antigen recurrence risk stratification.

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Section: Discussionmentioning

confidence: 99%

Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer

Ledezma¹,

Cifuentes²,

M³

et al. 2011

Asian J Androl

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“…34,35 Syndecan-1 is produced and shed from myeloma plasma cells and is involved in myeloma cell metastasis and growth. [36][37][38] A recent study also demonstrated that syndecans, including syndecan-1, directly bind to tumor cells and activate TACI signaling. 39 These studies may suggest that in contrast to BAFF, APRIL plays a nonredundant role in the survival of myeloma due to its interaction with syndecan-1 and possibly other HSPGs.…”

Section: Antimyeloma Response Of Atacicept and Baffr-ig In Scid-hu Micementioning

confidence: 96%

Atacicept (TACI-Ig) inhibits growth of TACIhigh primary myeloma cells in SCID-hu mice and in coculture with osteoclasts

Yaccoby

Pennisi

et al. 2007

Leukemia

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APRIL (a proliferation-inducing Ligand) and BLyS/BAFF (B-lymphocyte stimulator/B-cell-activating factor of the TNF (tumor necrosis factor) family have been shown to be the survival factors for certain myeloma cells in vitro. BAFF binds to the TNF-related receptors such as B-cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) and BAFFR, whereas APRIL binds to TACI and BCMA and to heparan sulfate proteoglycans (HSPG) such as syndecan-1. TACI gene expression in myeloma reportedly can distinguish tumors with a signature of microenvironment dependence (TACI high ) versus a plasmablastic signature (TACI low ). We tested the effect of atacicept (formerly TACI-Ig, which blocks APRIL and BAFF) and BAFFR-Ig (which blocks BAFF only) on primary myeloma growth in the SCID-hu model and in coculture with osteoclasts. With only few exceptions, atacicept and to a lesser extent BAFFR-Ig, inhibited growth of TACI high but not TACI low myeloma samples in vivo and ex vivo, and the response rate was inversely correlated with TACI expression. Most TACI high myeloma cells were molecularly classified as being low risk with our recently described 70-gene model. APRIL and BAFF were highly expressed by osteoclasts and were upregulated in myeloma cells after coculture with osteoclasts. Our findings suggest that APRIL plays an essential role in the survival of TACI high bone marrow-dependent myeloma cells and TACI gene expression may be a useful predictive marker for patients who could benefit from atacicept treatment.

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“…Heparan sulfate proteoglycans (HSPGs) are an important constituent in the tumor microenvironment [29][30][31]. The heparan sulfate degrading enzymes heparanase, hyalorunon and its receptor CD44 are shown to be up-regulated in many tumor types.…”

Section: Microenvironment Of Primary Breast and Prostate Cancersmentioning

confidence: 99%

“…Emerging data indicate that functional regulation of HSPGs occurs at heparin sulfate synthesis and enzymes that selectively cleave HSPG's components [30]. Physiological shedding of syndecan-1 by MMP-7 or MT1-MMP facilitates syndecan-1 dependent regulation of the inflammatory response, which may alter the tumor microenvironment.…”

Section: Microenvironment Of Primary Breast and Prostate Cancersmentioning

confidence: 99%

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Proteases as modulators of tumor–stromal interaction: Primary tumors to bone metastases

Wilson

Singh

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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SummaryAs cells undergo oncogenic transformation and as transformed cells arrive at metastatic sites, a complex interplay occurs with the surrounding stroma. This dialogue between tumor and stroma ultimately dictates the success of the tumor cells in the given microenvironment. As a result, understanding the molecular mechanisms at work is important for developing new therapeutic modalities. Proteases are major players in the interaction between tumor and stroma. This review will focus on the role of proteases in modulating tumor-stromal interactions of both primary breast and prostate tumors as well as at bone metastatic sites in a way that favors tumor growth.

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Enzymatic remodeling of heparan sulfate proteoglycans within the tumor microenvironment: Growth regulation and the prospect of new cancer therapies

Cited by 140 publications

References 58 publications

Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer

Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer

Atacicept (TACI-Ig) inhibits growth of TACIhigh primary myeloma cells in SCID-hu mice and in coculture with osteoclasts

Proteases as modulators of tumor–stromal interaction: Primary tumors to bone metastases

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