Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours

Breznik, Barbara; Motaln, Helena; Turnšek, Tamara Lah

doi:10.1515/hsz-2016-0283

Cited by 38 publications

(35 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Their protein expression patterns gives an indication whether cathepsins B and X are also functionally involved in modulating GSC trafficking and GSC maintenance in the niches. GSC niches are regions in GBM tumors, where GSCs are surrounded by specific ECM proteins and stromal cells, predominantly endothelial cells and pericytes of vessels, macrophages, stromal fibroblasts and possibly other brain stromal components (Calabrese et al 2007 ; Breznik et al 2017b ; Roos et al 2017 ; Hira et al 2018a ). Juxtacrine signaling between endothelial cells and GBM cells (Calabrese et al 2007 ) is crucial to maintain the stem cell phenotype of GSCs (Zhu et al 2011 ; Schiffer et al 2014 ; Roos et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cysteine cathepsins, a group of lysosomal proteases belonging to the C1A family of papain-like proteases ( https://www.ebi.ac.uk/merops/ ) (Kramer et al 2017 ), have been shown to be associated with growth and invasive spread of GBM (Gondi et al 2004 ; Claes et al 2007 ; Gole et al 2012 ; Breznik et al 2017 a). Cysteine cathepsins B, X and K are involved in various processes of cancer progression, including therapeutic resistance (Olson and Joyce 2015 ) and apoptosis (Kenig et al 2011 ).…”

Section: Introductionmentioning

confidence: 99%

“…Cathepsin B activity in cancer progression was initially associated with pericellular initiation of proteolytic cascades (Gole et al 2012 ; Olson and Joyce 2015 ) and with direct degradation of ECM components (Lah et al 1989 ). Indirectly, cathepsin B affects invasive behavior of GBM cells by proteolytic processing of cytokines and growth factors, such as transforming growth factor β (TGF-β) (Breznik et al 2017a ; Mitrović et al 2017 ). Noteworthy, cathepsin B was also implicated in the cross-talk between GBM cells and endothelial cells (Rempel et al 2000 ; Calabrese et al 2007 ), involving SDF-1α signaling (Kenig et al 2010 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches

et al. 2018

Self Cite

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most lethal brain tumor also due to malignant and therapy-resistant GBM stem cells (GSCs) that are localized in protecting hypoxic GSC niches. Some members of the cysteine cathepsin family of proteases have been found to be upregulated in GBM. Cathepsin K gene expression is highly elevated in GBM tissue versus normal brain and it has been suggested to regulate GSC migration out of the niches. Here, we investigated the cellular distribution of cathepsins B, X and K in GBM tissue and whether these cathepsins are co-localized in GSC niches. Therefore, we determined expression of these cathepsins in serial paraffin sections of 14 human GBM samples and serial cryostat sections of two samples using immunohistochemistry and metabolic mapping of cathepsin activity using selective fluorogenic substrates. We detected cathepsins B, X and K in peri-arteriolar GSC niches in 9 out of 16 GBM samples, which were defined by co-expression of the GSC marker CD133, the niche marker stromal-derived factor-1α (SDF-1α) and smooth muscle actin as a marker for arterioles. The expression of cathepsin B and X was detected in stromal cells and cancer cells throughout the GBM sections, whereas cathepsin K expression was more restricted to arteriole-rich regions in the GBM sections. Metabolic mapping showed that cathepsin B, but not cathepsin K is active in GSC niches. On the basis of these findings, it is concluded that cathepsins B, X and K have distinct functions in GBM and that cathepsin K is the most likely GSC niche-related cathepsin of the three cathepsins investigated.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been reported that secreted cathepsin B, cathepsin L and cathepsin S could cleave the cell adhesion molecule E-cadherin, promoting cancer cell invasion into the surrounding tissue [ 147 ]. Additionally, cathepsins are also involved in the processing of cytokines and chemokines, showing their involvement in inflammation and cancer processes [ 148 , 149 , 150 ].…”

Section: Myc–a Key Player In the Tumor Microenvironment (Tme)mentioning

confidence: 99%

MYC as a Multifaceted Regulator of Tumor Microenvironment Leading to Metastasis

Meškytė

Keskas

Ciribilli

2020

IJMS

View full text Add to dashboard Cite

The Myc family of oncogenes is deregulated in many types of cancer, and their over-expression is often correlated with poor prognosis. The Myc family members are transcription factors that can coordinate the expression of thousands of genes. Among them, c-Myc (MYC) is the gene most strongly associated with cancer, and it is the focus of this review. It regulates the expression of genes involved in cell proliferation, growth, differentiation, self-renewal, survival, metabolism, protein synthesis, and apoptosis. More recently, novel studies have shown that MYC plays a role not only in tumor initiation and growth but also has a broader spectrum of functions in tumor progression. MYC contributes to angiogenesis, immune evasion, invasion, and migration, which all lead to distant metastasis. Moreover, MYC is able to promote tumor growth and aggressiveness by recruiting stromal and tumor-infiltrating cells. In this review, we will dissect all of these novel functions and their involvement in the crosstalk between tumor and host, which have demonstrated that MYC is undoubtedly the master regulator of the tumor microenvironment. In sum, a better understanding of MYC’s role in the tumor microenvironment and metastasis development is crucial in proposing novel and effective cancer treatment strategies.

show abstract

“…Firstly, with the metastatic feature of decrease in adhesive force and increase in superficial charges, cancer cells could separate from the initial tumor. Through releasing numerous proteolytic enzymes and other factors, they possess the abilities of penetrating basement membrane (BM) and destroying cellular matrix, thus infiltrating into peripheral tissue [5]. After cancer enters the vascular and lymphatic vessels, these tumor cells survive and spread across the body through the circulatory system.…”

Section: Introductionmentioning

confidence: 99%

Effects of Xuefu Zhuyu Decoction on Cell Migration and Ocular Tumor Invasion inDrosophila

Wang

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Xuefu Zhuyu Decoction (XFZYD), a Traditional Chinese Medicine (TCM) decoction mainly for treating blood stasis syndrome, has been widely investigated and applied in clinic and in laboratory. XFZYD contains 11 herbs and has been identified to promoting blood circulation to remove blood stasis for cardiovascular disease. Meanwhile, blood stasis is directly related to malignant tumor according to TCM basic theory. However, the effects of XFZYD on tumor metastasis and the underlying mechanisms are still largely unknown. Here, we employed well-established Drosophila cell migration and tumor invasion models to explore whether XFZYD has the anticancer activity on tumor metastasis in vivo. Our work has demonstrated that XFZYD could suppress cell migration and tumor invasion at the moderate concentrations. In addition, XFZYD altered the expression of MMP1, β-integrin, and E-cadherin to impede cell migration. Moreover, XFZYD inhibited ocular tumor invasion presumably by reducing the activity of Notch signaling. Together, these evidences reveal a positive role of XFZYD in suppressing cell migration and tumor metastasis, providing the potential drug targets and key clues for cancer clinical treatment strategies.

show abstract

Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours

Cited by 38 publications

References 60 publications

Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches

Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches

MYC as a Multifaceted Regulator of Tumor Microenvironment Leading to Metastasis

Effects of Xuefu Zhuyu Decoction on Cell Migration and Ocular Tumor Invasion inDrosophila

Contact Info

Product

Resources

About