Ovarian Cells Have Increased Proliferation in Response to Heparin-Binding Epidermal Growth Factor as Collagen Density Increases

Fogg, Kaitlin C.; Renner, Carine; Christian, Hannah; Walker, Alyssa; Marty-Santos, Leilani; Khan, Aisha; Olson, Will R.; Parent, Carl; O'Shea, Amy; Wellik, Deneen M.; Weisman, Paul; Kreeger, Pamela K.

doi:10.1089/ten.tea.2020.0001

Cited by 20 publications

(18 citation statements)

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“…This region stained positive for both fibronectin and collagen type I. Dot blots of benign human omentum 34 indicated a ratio of fibronectin to collagen I in this region of 0.25:100 to 0.5:100. Scale bar: 100 μ m. …”

Section: Figmentioning

confidence: 89%

“…The use of collagen I and fibronectin was motivated by immunofluorescent staining showing the presence of these proteins in the mesothelial layer of benign human omentum ( Fig. 13 ), and prior dot blots 34 that indicated a ratio of fibronectin to collagen I of 0.25:100 to 0.5:100. Phase contrast images were captured every 10 min for 24 h, and cell velocities were computed by applying Fast Iterative Digital Image Correlation.…”

Section: Methodsmentioning

confidence: 99%

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Topological defects in the mesothelium suppress ovarian cancer cell clearance

et al. 2021

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We investigated an in vitro model for mesothelial clearance, wherein ovarian cancer cells invade into a layer of mesothelial cells, resulting in mesothelial retraction combined with cancer cell disaggregation and spreading. Prior to the addition of tumor cells, the mesothelial cells had an elongated morphology, causing them to align with their neighbors into well-ordered domains. Flaws in this alignment, which occur at topological defects, have been associated with altered cell density, motion, and forces. Here, we identified topological defects in the mesothelial layer and showed how they affected local cell density by producing a net flow of cells inward or outward, depending on the defect type. At locations of net inward flow, mesothelial clearance was impeded. Hence, the collective behavior of the mesothelial cells, as governed by the topological defects, affected tumor cell clearance and spreading. Importantly, our findings were consistent across multiple ovarian cancer cell types, suggesting a new physical mechanism that could impact ovarian cancer metastasis.

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Section: Figmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Topological defects in the mesothelium suppress ovarian cancer cell clearance

et al. 2021

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“…Increasing the density of collagen I gels resulted in a loss of ductal-like morphology for breast cancer cells and increased glutamine entry into the TCA cycle, suggesting a role for the ECM in energy regulation (Morris et al, 2016). When collagen I density was matched to in vivo levels in the normal omentum, ovarian cancer cells were insensitive to the growth factor HB-EGF (Fogg et al, 2020). In contrast, ovarian cancer cells proliferated in response to HB-EGF when cultured on gels matching the density of metastatic tumors in the omentum (Fogg et al, 2020).…”

Section: Ll Open Accessmentioning

confidence: 99%

“…When collagen I density was matched to in vivo levels in the normal omentum, ovarian cancer cells were insensitive to the growth factor HB-EGF (Fogg et al, 2020). In contrast, ovarian cancer cells proliferated in response to HB-EGF when cultured on gels matching the density of metastatic tumors in the omentum (Fogg et al, 2020). Changes in ECM density may also be mimicked by altering the concentration of ECM-derived peptides in synthetic scaffolds.…”

Section: Ll Open Accessmentioning

confidence: 99%

“…Characterization of the tumor ECM by immunohistochemical staining or RNA-based analysis has demonstrated that ECM composition around the primary tumor and metastatic sites undergoes radical changes during tumor progression. For example, many studies have documented upregulation of collagen I in primary breast, liver, lung, and esophageal tumors and in metastatic ovarian cancer (Fang et al, 2019;Fogg et al, 2020;van 't Veer et al, 2002;Zhang et al, 2018). Hyaluronic acid (HA) is also significantly elevated in a wide range of cancers (e.g., breast, prostate, bladder, colon) and is associated with an increased likelihood of metastasis and poor prognosis (Lokeshwar et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment

et al. 2020

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Clinical evidence supports a role for the extracellular matrix (ECM) in cancer risk and prognosis across multiple tumor types, and numerous studies have demonstrated that individual ECM components impact key hallmarks of tumor progression (e.g., proliferation, migration, angiogenesis). However, the ECM is a complex network of fibrillar proteins, glycoproteins, and proteoglycans that undergoes dramatic changes in composition and organization during tumor development. In this review, we will highlight how engineering approaches can be used to examine the impact of changes in tissue architecture, ECM composition (i.e., identity and levels of individual ECM components), and cellular-and tissue-level mechanics on tumor progression. In addition, we will discuss recently developed methods to model the ECM that have not yet been applied to the study of cancer.

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Quantitative Analysis of the Extracellular Matrix by Immunoblot

Fogg

2021

Methods in Molecular Biology

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Knowing the global and local concentration of extracellular matrix proteins provides critical information for building tissue engineered constructs of healthy and diseased tissue. Here we describe a method of integrating quantitative dot blot along with immunohistochemistry on the same patient sample in order to calculate the overall protein concentration as well as the concentration in a region of interest.

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Ovarian Cells Have Increased Proliferation in Response to Heparin-Binding Epidermal Growth Factor as Collagen Density Increases

Cited by 20 publications

References 50 publications

Topological defects in the mesothelium suppress ovarian cancer cell clearance

Topological defects in the mesothelium suppress ovarian cancer cell clearance

Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment

Quantitative Analysis of the Extracellular Matrix by Immunoblot

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