Maspin is not required for embryonic development or tumour suppression

Teoh, Sonia Soo Yee; Vieusseux, Jessica L.; Prakash, Monica D.; Berkowicz, Susan; Luu, Jennii; Bird, Catherina H.; Law, Ruby H. P.; Rosado, Carlos J.; Price, John T.; Whisstock, James C.; Bird, Phillip I.

doi:10.1038/ncomms4164

Cited by 30 publications

(36 citation statements)

References 54 publications

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“…In this way we demonstrated a direct interaction between maspin and -actin. The interaction between maspin and actin has been reported previously (Cella et al 2006) and also contended (Teoh et al 2014). This study supports the presence of an interacting relationship between maspin and actin.…”

Section: Discussionsupporting

confidence: 79%

Effects of Noninhibitory Serpin Maspin on the Actin Cytoskeleton: A Quantitative Image Modeling Approach

et al. 2016

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Section: Discussionsupporting

confidence: 79%

Effects of Noninhibitory Serpin Maspin on the Actin Cytoskeleton: A Quantitative Image Modeling Approach

et al. 2016

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“…Most recently, data have emerged that pose new questions related to the role of endogenously expressed Maspin in biology and disease (50). While our study has focused on understanding the internalization and trafficking of exogenously applied rMaspin, we hope it will contribute new insights pertinent to the findings of previous reports.…”

Section: Discussionmentioning

confidence: 99%

Internalization by Multiple Endocytic Pathways and Lysosomal Processing Impact Maspin-Based Therapeutics

Bodenstine

Seftor

et al. 2014

Molecular Cancer Research

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Patients with metastatic disease face high rates of mortality with a paucity of therapeutic options. Protein-based therapeutics provides advantages over traditional chemotherapy through increased specificity, decreased immune responses and more direct means of delivery. However, development is often hindered due to insufficient knowledge regarding proteolytic processing by cells when exogenously applied. This study focuses on recombinant Maspin (rMaspin), a serine protease inhibitor (SERPINB5), which alters invasive properties when directly applied to cancer cells. Previous evidence suggests differences in the effects of rMaspin treatment when compared to endogenous re-expression, with little explanation for these discrepancies. A leading hypothesis is that exogenously applied rMaspin is subject to different regulatory and/or processing mechanisms in cancer cells when compared to endogenous expression. Therefore, a more detailed understanding of the mechanisms of internalization and subcellular trafficking of rMaspin is needed to guide future translational development. We describe the molecular trafficking of rMaspin in cytoplasmic vesicles of the endosomal/lysosomal pathway and characterize its uptake by multiple endocytic mechanisms. Time-lapse laser scanning confocal microscopy shows the uptake, in real-time, of dye labeled rMaspin in cancer cells. This study indicates that cellular processing of rMaspin plays a key role affecting its biological activity and highlights the need for new approaches aimed at increasing the availability of rMaspin when used to treat cancer.

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“…But still the extracellular presence of maspin is in debate according to a recent study, where it has been stated that maspin has no influence on tumor growth and embryonic development (Teoh et al, 2014). These motivated us to extend our previous cellular level model with cell-cell adhesion and cell-ECM interaction to define how maspin reduces cell migration by showing potential enhancement with ECM components (fibronectin, laminin, collagen etc.…”

Section: Biological Backgroundmentioning

confidence: 99%

An in silico model to demonstrate the effects of Maspin on cancer cell dynamics

Al-Mamun

Farid

Ravenhil

et al. 2016

Journal of Theoretical Biology

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Most cancer treatments efficacy depends on tumor metastasis suppression, where tumor suppressor genes play an important role. Maspin (Mammary Serine Protease Inhibitor), an non-inhibitory serpin has been reported as a potential tumor suppressor to influence cell migration, adhesion, proliferation and apoptosis in in vitro and in vivo experiments in last two decades. Lack of computational investigations hinders its ability to go through clinical trials. Previously, we reported first computational model for maspin effects on tumor growth using artificial neural network and cellular automata paradigm with in vitro data support.This paper extends the previous in silico model by encompassing how maspin influences cell migration and the cell-extracellular matrix interaction in subcellular level. A feedforward neural network was used to define each cell behavior (proliferation, quiescence, apoptosis) which followed a cell-cycle algorithm to show the microenvironment impacts over tumor growth. Furthermore, the model concentrates how the in silico experiments results can further confirm the fact that maspin reduces cell migration using specific in vitro data verification method. The data collected from in vitro and in silico experiments formulates an unsupervised learning problem which can be solved by using different clustering algorithms. A density based clustering technique was developed to measure the similarity between two datasets based on the number of links between instances. Our proposed clustering algorithm first finds the nearest neighbors of each instance, and then redefines the similarity between pairs of instances in terms of how many nearest neighbors share the two instances. The number of links between two instances is defined as the number of common neighbors they have. The results showed significant resemblances with in vitro experimental data. The results also offer a new insight into the dynamics of maspin and establish as a metastasis suppressor gene for further molecular research.

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Maspin is not required for embryonic development or tumour suppression

Cited by 30 publications

References 54 publications

Effects of Noninhibitory Serpin Maspin on the Actin Cytoskeleton: A Quantitative Image Modeling Approach

Effects of Noninhibitory Serpin Maspin on the Actin Cytoskeleton: A Quantitative Image Modeling Approach

Internalization by Multiple Endocytic Pathways and Lysosomal Processing Impact Maspin-Based Therapeutics

An in silico model to demonstrate the effects of Maspin on cancer cell dynamics

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