Roles of Pericellular Proteases in Tumor Angiogenesis: Therapeutic Implications

Kraniak, Janice M.; Mattingly, Raymond R.; Sloane, Bonnie F.

doi:10.1002/9781119300229.ch14

Cited by 2 publications

(4 citation statements)

References 191 publications

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“…Although it is the work of multiple proteinases interacting with companion proteins that create a favorable environment for invasion and metastasis, the degradation of collagen IV is part of the process. MMP2 (gelatinase A) enhances the cleavage of collagen IV by MMP9 (gelatinase B) (Kraniak et al, 2018). We therefore assayed the ability of NF1 PN cells to degrade their ECM in comparison to that of wild-type SCs to determine whether this invasive phenotype could be assayed in vitro .…”

Section: Resultsmentioning

confidence: 99%

“…The increase in matrix proteolytic activity (capacity to degrade collagen IV) observed in the 3D cultures of NF1 PN cells as compared to control cultures of SCs may be highly significant and translatable to human tissues (Kraniak et al, 2018). First, these results confirm original observations that found that SCs derived from human neurofibromas were highly invasive and secreted much more matrix metalloprotease-2 (a gelatinase) than control human SCs (Muir, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening

Kraniak

Chalasani

Wallace

et al. 2018

Experimental Neurology

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Plexiform neurofibromas (PNs), which may be present at birth in up to half of children with type 1 neurofibromatosis (NF1), can cause serious loss of function, such as quadriparesis, and can undergo malignant transformation. Surgery is the first line treatment although the invasive nature of these tumors often prevents complete resection. Recent clinical trials have shown promising success for some drugs, notably selumetinib, an inhibitor of MAP kinase kinase (MEK). We have developed three-dimensional (3D) cell culture models of immortalized cells from NF1 PNs and of control Schwann cells (SCs) that we believe mimic more closely the in vivo condition than conventional two-dimensional (2D) cell culture. Our goal is to facilitate pre-clinical identification of potential targeted therapeutics for these tumors. Three drugs, selumetinib (a MEK inhibitor), picropodophyllin (an IGF-1R inhibitor) and LDN-193189 (a BMP2 inhibitor) were tested with dose-response design in both 2D and 3D cultures for their abilities to block net cell growth. Cell lines grown in 3D conditions showed varying degrees of resistance to the inhibitory actions of all three drugs. For example, control SCs became resistant to growth inhibition by selumetinib in 3D culture. LDN-193189 was the most effective drug in 3D cultures, with only slightly reduced potency compared to the 2D cultures. Characterization of these models also demonstrated increased proteolysis of collagen IV in the matrix by the PN driver cells as compared to wild-type SCs. The proteolytic capacity of the PN cells in the model may be a clinically significant property that can be used for testing the ability of drugs to inhibit their invasive phenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening

Kraniak

Chalasani

Wallace

et al. 2018

Experimental Neurology

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“…For example, stem/progenitor cells could secret EVs containing angiogenic GFs (e.g., bFGF, PDGF, TGF‐β, and VEGF) (Table 1). 38 In addition to GFs, the neovascularisation process may be improved via particular kinds of enzymes, including tissue‐type plasminogen activator (tPA), urokinase‐type plasminogen activator (uPA), and matrix metallopeptidases (MMPs) 39 . Over the last years, several published works have highlighted the critical role of miRNAs, that is, small non‐coding RNAs with a length of 19–23 nucleotides, in promoting angiogenesis 40 …”

Section: Role Of Stem Cells In Angiogenesis: a Short Surveymentioning

confidence: 99%

“…38 In addition to GFs, the neovascularisation process may be improved via particular kinds of enzymes, including tissue-type plasminogen activator (tPA), urokinasetype plasminogen activator (uPA), and matrix metallopeptidases (MMPs). 39 Over the last years, several published works have highlighted the critical role of miRNAs, that is, small non-coding RNAs with a length of 19-23 nucleotides, in promoting angiogenesis. 40 In the following sections, the pro-angiogenic potentials of different types of stem/progenitor cells are introduced and compared, discussing their usefulness in accelerating wound healing.…”

Section: Role Of Stem Cells In Angiogenesis: a Short Surveymentioning

confidence: 99%

Stem cell‐mediated angiogenesis in skin tissue engineering and wound healing

Azari

Nazarnezhad

Webster

et al. 2022

Wound Repair Regeneration

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The timely management of skin wounds has been an unmet clinical need for centuries.While there have been several attempts to accelerate wound healing and reduce the cost of hospitalisation and the healthcare burden, there remains a lack of efficient and effective wound healing approaches. In this regard, stem cell-based therapies have garnered an outstanding position for the treatment of both acute and chronic skin wounds. Stem cells of different origins (e.g., embryo-derived stem cells) have been utilised for managing cutaneous lesions; specifically, mesenchymal stem cells (MSCs) isolated from foetal (umbilical cord) and adult (bone marrow) tissues paved the way to more satisfactory outcomes. Since angiogenesis plays a critical role in all four stages of normal wound healing, recent therapeutic approaches have focused on utilising stem cells for inducing neovascularisation. In fact, stem cells can promote angiogenesis via either differentiation into endothelial lineages or secreting pro-angiogenic exosomes.Furthermore, particular conditions (e.g., hypoxic environments) can be applied in order to boost the pro-angiogenic capability of stem cells before transplantation. For tissue engineering and regenerative medicine applications, stem cells can be combined with specific types of pro-angiogenic biocompatible materials (e.g., bioactive glasses) to enhance the neovascularisation process and subsequently accelerate wound healing.As such, this review article summarises such efforts emphasising the bright future that is conceivable when using pro-angiogenic stem cells for treating acute and chronic skin wounds.

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Roles of Pericellular Proteases in Tumor Angiogenesis: Therapeutic Implications

Cited by 2 publications

References 191 publications

Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening

Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening

Stem cell‐mediated angiogenesis in skin tissue engineering and wound healing

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