Differential effects of EGF gradient profiles on MDA-MB-231 breast cancer cell chemotaxis

Wang, Shur-Jen; Saadi, Wajeeh; Lin, Francis; Nguyen, C.; Jeon, Noo Li

doi:10.1016/j.yexcr.2004.06.030

Cited by 248 publications

(262 citation statements)

References 33 publications

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“…The most malignant cell line, the triple-negative MDA-MB-231 (48,49), exhibited the highest F-HA binding and Het.I. To determine whether these two parameters were functionally linked to malignancy, we took advantage of our ability to revert MDA-MB-231 cells to a more nonmalignant phenotype by ablating β1 integrin and PI3K signaling in 3D culture (57).…”

Section: Resultsmentioning

confidence: 99%

“…Primary breast tumors and most BCa lines group into subtypes, with different hormone receptor levels and human epidermal growth factor receptor-2 (HER2) expression (44)(45)(46)(47). Triple-negative BCa is estrogen receptor-negative (ER − ), progesterone receptor-negative (PR − ) and HER2 − , and is currently one of the most difficult BCa to treat because it is commonly chemoresistant and exhibits early metastases with consequent poor 5-y survival rates (48)(49)(50)(51)(52). Few of these BCa subtypes have been characterized for CD44 or RHAMM expression (31,53,54), and none to our knowledge have been examined for HA binding.…”

Section: Resultsmentioning

confidence: 99%

“…2). We used MDA-MB-231 cells because these coexpress CD44 and RHAMM, exhibit the highest F-HA binding and heterogeneity, and are widely used as a malignant triple-negative BCa model (48)(49)(50)(51)(52).…”

Section: Resultsmentioning

confidence: 99%

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Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but slow-growing breast tumor subset

Veiseh

Kwon

Borowsky

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Tumor heterogeneity confounds cancer diagnosis and the outcome of therapy, necessitating analysis of tumor cell subsets within the tumor mass. Elevated expression of hyaluronan (HA) and HA receptors, receptor for HA-mediated motility (RHAMM)/HA-mediated motility receptor and cluster designation 44 (CD44), in breast tumors correlates with poor outcome. We hypothesized that a probe for detecting HA-HA receptor interactions may reveal breast cancer (BCa) cell heterogeneity relevant to tumor progression. A fluorescent HA (F-HA) probe containing a mixture of polymer sizes typical of tumor microenvironments (10-480 kDa), multiplexed profiling, and flow cytometry were used to monitor HA binding to BCa cell lines of different molecular subtypes. Formulae were developed to quantify binding heterogeneity and to measure invasion in vivo. Two subsets exhibiting differential binding (HA −/low vs. HA high ) were isolated and characterized for morphology, growth, and invasion in culture and as xenografts in vivo. F-HA-binding amounts and degree of heterogeneity varied with BCa subtype, were highest in the malignant basal-like cell lines, and decreased upon reversion to a nonmalignant phenotype. Binding amounts correlated with CD44 and RHAMM displayed but binding heterogeneity appeared to arise from a differential ability of HA receptor-positive subpopulations to interact with F-HA. HA high subpopulations exhibited significantly higher local invasion and lung micrometastases but, unexpectedly, lower proliferation than either unsorted parental cells or the HA −/low subpopulation. Querying F-HA binding to aggressive tumor cells reveals a previously undetected form of heterogeneity that predicts invasive/metastatic behavior and that may aid both early identification of cancer patients susceptible to metastasis, and detection/therapy of invasive BCa subpopulations.tumor cell heterogeneity | hyaluronan binding | heterogeneity index B reast tumors display substantial heterogeneity driven by genetic and epigenetic mechanisms (1-3). These processes select and support tumor cell subpopulations with distinct phenotypes in proliferation, metastatic/invasive proclivity, and treatment susceptibility that contribute to clinical outcomes. Currently, there is a paucity of biomarkers to identify these subpopulations (3-12). Although detection of genetic heterogeneity may itself be a breast cancer (BCa) prognostic marker (3, 13-15), the phenotypes manifested from this diversity are context-dependent. Therefore, phenotypic markers provide additional powerful tools for biological information required to design diagnostics and therapeutics. Glycomic approaches have enormous potential for revealing tumor cell phenotypic heterogeneity because glycans are themselves highly heterogeneous and their complexity reflects the nutritional, microenvironmental, and genetic dynamics of the tumors (16-18).We used hyaluronan (HA) as a model carbohydrate ligand for probing heterogeneity in glycosaminoglycan-BCa cell receptor interactions. We reasoned this approach...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but slow-growing breast tumor subset

Veiseh

Kwon

Borowsky

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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“…Classically, the formation of such a gradient involves a "source" that continuously produces a signal that freely diffuses through extracellular space and a "sink" that actively eliminates it (3)(4)(5)(6). To study cellular responses, investigators have artificially created chemical gradients in vitro using gels (7,8), micropipettes (9), and microfluidic devices (10)(11)(12). However, endogenous gradients are challenging to measure directly.…”

mentioning

confidence: 99%

Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

Cai

Dai

Prasad

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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A long-standing question in collective cell migration has been what might be the relative advantage of forming a cluster over migrating individually. Does an increase in the size of a collectively migrating group of cells enable them to sample the chemical gradient over a greater distance because the difference between front and rear of a cluster would be greater than for single cells? We combined theoretical modeling with experiments to study collective migration of the border cells in-between nurse cells in the Drosophila egg chamber. We discovered that cluster size is positively correlated with migration speed, up to a particular point above which speed plummets. This may be due to the effect of viscous drag from surrounding nurse cells together with confinement of all of the cells within a stiff extracellular matrix. The model predicts no relationship between cluster size and velocity for cells moving on a flat surface, in contrast to movement within a 3D environment. Our analyses also suggest that the overall chemoattractant profile in the egg chamber is likely to be exponential, with the highest concentration in the oocyte. These findings provide insights into collective chemotaxis by combining theoretical modeling with experimentation.cell migration | theoretical modeling | three-dimensional | chemotaxis

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“…Concentration gradients of chemical reagents play important roles in cell biology studies [1][2][3]. Conventionally, the Boyden chambers, pipettes and gels are used to create concentration gradients of chemicals.…”

Section: Introductionmentioning

confidence: 99%

Design synthesis and experimental validation of microfluidic concentration gradient generators

Zhou

Wang

Mukherjee

et al. 2008

2008 IEEE 21st International Conference on Micro Electro Mechanical Systems

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This paper presents a synthesis method and its experimental validation for microfluidic concentration gradient generators that use multi-stream laminar flow. The method is based on an iterative framework in which designs are evaluated with an analytical convection-diffusion model. Comparing to the expensive trial-and-error experimentation or the time consuming finite element simulation, this design scheme enables the efficient design of concentration gradient generators capable of generating complex concentration profiles. We describe the synthesis method, and validate it by experiments with devices that are designed based on the method. The concentration profiles obtained from the experiments agree well with the prescribed ones.

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Differential effects of EGF gradient profiles on MDA-MB-231 breast cancer cell chemotaxis

Cited by 248 publications

References 33 publications

Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but slow-growing breast tumor subset

Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but slow-growing breast tumor subset

Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

Design synthesis and experimental validation of microfluidic concentration gradient generators

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