<i>In vitro</i> elucidation of the role of pericellular matrix in metastatic extravasation and invasion of breast carcinoma cells

Brett, Marie Elena; Bomberger, Heather E.; Doak, Geneva R.; Price, Matthew A.; McCarthy, James B.; Wood, David E.

doi:10.1039/c7ib00173h

Cited by 18 publications

(16 citation statements)

References 31 publications

(45 reference statements)

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“…Finally, we utilized a microfluidic model of hematopoietic cell -endothelial cell interactions in which the hematopoietic cells were in a state of flow through an "artificial vessel" which would better mimic the microenvironment compared to traditional transwell experiments 38 . We produced an HDMEC-endothelialized lumen on a microscaffold through which GFP + linhematopoietic cells were flowed and direct live-cell imaging of the cells binding to the artificial vascular wall was performed (Figure 4G).…”

Section: Resultsmentioning

confidence: 99%

An irradiated marrow niche reveals a small non-collagenous protein mediator of homing, dermatopontin

et al. 2021

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Hematopoietic cell homing after hematopoietic cell transplant (HCT) is governed by several pathways involving marrow niche cells that are evoked after pre-HCT conditioning. To understand the factors that play a role in homing, we performed expression analysis on the zebrafish marrow niche cells following conditioning. We determined that the non-collagenous protein extracellular matrix related protein dermatopontin (Dpt) was upregulated seven-fold in response to irradiation. Studies in mice revealed DPT induction both with radiation and lipopolysaccharide exposure. Interestingly, we found that co-incubation of zebrafish or murine hematopoietic cells with rDPT impedes hematopoietic stem and progenitor cell homing by 50% and 86%, respectively. Similarly, this translated into a 24% reduction in long term engraftment (versus control, p = 0.01). We found DPT to interact with VLA-4 and block hematopoietic - endothelial cell adhesion and transendothelial migration. Finally, a DPT knockout mouse displayed a 60% increase in homing of hematopoietic cells versus wildtype (p = 0.03) with slight improvement in long-term LSK-SLAM engraftment (2-fold, p = 0.04). These data show that the extracellular matrix (ECM)-related protein DPT increases with radiation and transiently impedes the transendothelial migration of hematopoietic cells to the marrow.

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Section: Resultsmentioning

confidence: 99%

An irradiated marrow niche reveals a small non-collagenous protein mediator of homing, dermatopontin

et al. 2021

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“…Besides investigating the effects of cell deformation, microfluidic models were exploited to distinguish the extravasation ability of cancer cells with a different degree of malignancy (Chen et al, 2013 ) as well as of cancer cells originating from different primary tumors (Tourovskaia et al, 2014 ). For instance, the presence of hyaluronan in the pericellular matrix of breast cancer cells (Brett et al, 2018 ) or the expression of specific proteins implicated in brain cancer development (Liu et al, 2019 ) were studied in relation to the metastatic potential of cancer cells, demonstrating that microfluidic extravasation models are able to capture differences in cell malignancy and allow identifying some of the elements responsible of a high metastatic potential. Breast cancer cells with different metastatic potential were also pre-conditioned in hypoxic conditions before injection in a microfluidic device, demonstrating that hypoxic cells have a higher extravasation rate compared to normoxic cells (Song et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Advanced Microfluidic Models of Cancer and Immune Cell Extravasation: A Systematic Review of the Literature

Mondadori

Crippa

Moretti

et al. 2020

Front. Bioeng. Biotechnol.

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Extravasation is a multi-step process implicated in many physiological and pathological events. This process is essential to get leukocytes to the site of injury or infection but is also one of the main steps in the metastatic cascade in which cancer cells leave the primary tumor and migrate to target sites through the vascular route. In this perspective, extravasation is a double-edged sword. This systematic review analyzes microfluidic 3D models that have been designed to investigate the extravasation of cancer and immune cells. The purpose of this systematic review is to provide an exhaustive summary of the advanced microfluidic 3D models that have been designed to study the extravasation of cancer and immune cells, offering a perspective on the current state-of-the-art. To this end, we set the literature search cross-examining PUBMED and EMBASE databases up to January 2020 and further included non-indexed references reported in relevant reviews. The inclusion criteria were defined in agreement between all the investigators, aimed at identifying studies which investigate the extravasation process of cancer cells and/or leukocytes in microfluidic platforms. Twenty seven studies among 174 examined each step of the extravasation process exploiting 3D microfluidic devices and hence were included in our review. The analysis of the results obtained with the use of microfluidic models allowed highlighting shared features and differences in the extravasation of immune and cancer cells, in view of the setup of a common framework, that could be beneficial for the development of therapeutic approaches fostering or hindering the extravasation process.

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“…Cellular adhesion assays were performed as previously described [22]. Briefly, the microfluidic model was fabricated using standard soft lithography of polydimethylsiloxane (PDMS) (#4019862, Ellsworth).…”

Section: Methodsmentioning

confidence: 99%

SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis

Smeester

Slipek

Pomeroy

et al. 2019

Preprint

Self Cite

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47Semaphorins, specifically type IV, are important regulators of axonal guidance and 48 have been increasingly implicated in poor prognoses in a number of different solid 49 cancers. In conjunction with their cognate PLXNB family receptors, type IV members have 50 been increasingly shown to mediate oncogenic functions necessary for tumor 51 development and malignant spread. In this study, we investigated the role of semaphorin 52 4C (SEMA4C) in osteosarcoma growth, progression, and metastasis. We investigated 53 the expression and localization of SEMA4C in primary osteosarcoma patient tissues and 54 its tumorigenic functions in these malignancies. We demonstrate that overexpression of 55 SEMA4C promotes properties of cellular transformation, while RNAi knockdown of 56 SEMA4C promotes adhesion and reduces cellular proliferation, colony formation, 57 migration, wound healing, tumor growth, and lung metastasis. These phenotypic changes 58 were accompanied by reductions in activated AKT signaling, G1 cell cycle delay, and 59 decreases in expression of mesenchymal marker genes SNAI1, SNAI2, and TWIST1. 60Lastly, monoclonal antibody blockade of SEMA4C in vitro mirrored that of the genetic 61 studies. Together, our results indicate a multi-dimensional oncogenic role for SEMA4C in 62 metastatic osteosarcoma and more importantly that SEMA4C has actionable clinical 63 potential. 64 65 Introduction 66Osteosarcoma is a malignant, primarily pediatric tumor, of the growing long bones 67 with peak incidence in the second decade of life [1]. Derived from mesenchymal origins 68 in the pre-osteoblastic lineage, osteosarcomas arise from the failure of osteoblasts to 69 differentiate into mature bone-building cells [2]. Osteosarcomas are commonly typified by 70 their heterogeneity, genomic instability, and frequency of systemic metastasis primarily 71 to the lungs [3, 4]. Despite advances in chemotherapy regimens and surgical resection, 72 survival rates for patients with osteosarcoma have remained stagnant for more than four 73 decades [5]. The complex nature of osteosarcoma presents unique difficulties with 74 respect to elucidating novel therapeutic targets and identifying treatment strategies that 75 may prove most effective, particularly across individual patients. Given this, it is critically 76 important to better understand not only the mechanisms specific to osteosarcoma 77 development and progression, but most importantly metastasis, in order to develop better 78 treatment options for patients with this devastating disease. 79 Semaphorins are a family of membrane-bound and soluble proteins that modulate 80 a whole host of cellular functions including differentiation, cytoskeletal rearrangement, 81 and motility [6]. Interestingly, semaphorin family members have been reported to mediate 82 many hallmarks of cancer including cellular proliferation, angiogenesis, and immune 83 escape [7-9]. Recent evidence from studies of the SEMA4-PLXNB family of axonal 84 guidance molecules in normal bone cells suggests that osteoclastic exp...

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In vitro elucidation of the role of pericellular matrix in metastatic extravasation and invasion of breast carcinoma cells

Cited by 18 publications

References 31 publications

An irradiated marrow niche reveals a small non-collagenous protein mediator of homing, dermatopontin

An irradiated marrow niche reveals a small non-collagenous protein mediator of homing, dermatopontin

Advanced Microfluidic Models of Cancer and Immune Cell Extravasation: A Systematic Review of the Literature

SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis

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