Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion

Liang, Shuang; Slattery, Margaret J.; Dong, Chuan

doi:10.1016/j.yexcr.2005.07.028

Cited by 62 publications

(83 citation statements)

References 40 publications

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“…In addition, constitutive secretion of the chemokine IL-8 from melanoma cells, as well as the capacity of increased IL-8 production from a melanoma-PMN microenvironment, was significantly decreased following inhibition of mutant V600E B-Raf. Coupling these observations with previous studies showing that endogenously produced IL-8 and ICAM-1-h 2 integrin binding mediate melanoma extravasation (11,12) provides a rationale and mechanistic basis for targeting mutant V600E B-Raf to inhibit melanoma extravasation and subsequent metastasis development. Scott Simon, University of California Davis, Davis, CA) and were maintained in culture as previously described (17).…”

Section: Introductionsupporting

confidence: 62%

“…Previous studies have shown that human PMN facilitates melanoma extravasation in vitro (11,12). To investigate the interaction of melanoma cells with mouse PMNs, colocalization of green GFP-tagged melanoma cells and red phycoerythrin-tagged mouse PMNs in the lungs was studied.…”

Section: Resultsmentioning

confidence: 99%

“…1; refs. 11,12). Endogenous interleukin 8 (IL-8) secreted by melanoma cells also increases h 2 integrin expression on PMNs and modulates PMN-facilitated melanoma extravasation (12).…”

Section: Introductionmentioning

confidence: 99%

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Targeting Mutant (V600E)B-Rafin Melanoma Interrupts Immunoediting of Leukocyte Functions and Melanoma Extravasation

Liang¹,

Sharma²,

Peng

et al. 2007

Cancer Research

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Polymorphonuclear neutrophils (PMN) facilitate melanoma cell extravasation under dynamic flow conditions by the binding of intercellular adhesion molecule-1 (ICAM-1) on melanoma cells to B 2 integrins on PMNs, which is mediated by endogenously produced chemokine interleukin 8 (IL-8) from the tumor microenvironment. However, little is known about the role of B-Raf, the most mutated gene in malignant melanomas, in this process. In this study, we investigated the functional importance of B-Raf in melanoma extravasation by using short interfering RNA to reduce expression/ activity of mutant V600E B-Raf in melanoma. Results indicated that knockdown of mutant V600E B-Raf inhibited melanoma cell extravasation in vitro and subsequent lung metastasis development in vivo. Mechanistic studies showed that inhibition of V600E B-Raf significantly reduced the constitutive secretion of IL-8 from melanoma cells as well as the capacity of endogenous IL-8 production from the melanoma-PMN microenvironment. Furthermore, a reduction in ICAM-1 expression on melanoma cells was detected following mutant V600E B-Raf knockdown. Together, these results suggest that targeting mutant V600E B-Raf reduces melanoma cell extravasation by decreasing IL-8 production and interrupting ICAM-1-B 2 integrin binding of melanoma cells to the endothelium mediated by PMNs in the microcirculation, which provides a rationale and mechanistic basis for targeting mutant V600E BRaf to inhibit melanoma extravasation and subsequent metastasis development. [Cancer Res 2007;67(12):5814-20]

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Section: Introductionsupporting

confidence: 62%

Section: Resultsmentioning

confidence: 99%

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Targeting Mutant (V600E)B-Rafin Melanoma Interrupts Immunoediting of Leukocyte Functions and Melanoma Extravasation

Liang¹,

Sharma²,

Peng

et al. 2007

Cancer Research

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“…We have shown that V600E B-Raf plays a critical role regulating both of these processes thereby regulating metastasis. Interaction of melanoma cells with neutrophils facilitates attachment to the endothelium, thereby promoting extravasation into lung stroma (52,53). We have provided novel insight into these processes showing that, in melanoma, V600E B-Raf promotes metastasis by facilitating extravasation across the endothelial layer under flow conditions and by conferring increased proliferative potential in the lung microenvironment.…”

Section: Discussionmentioning

confidence: 98%

“…B-Raf enhanced extravasation by facilitating interaction with neutrophils, which aided in tethering the melanoma cell to the endothelial lining under flow conditions, thereby promoting movement of the melanoma cell through the endothelial lining (52,53). Once extravasation has occurred into lung stroma, cells need to proliferate, also facilitated by V600E B-Raf.…”

Section: V600ementioning

confidence: 99%

Targeting Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Kinase in the Mutant (V600E) B-Raf Signaling Cascade Effectively Inhibits Melanoma Lung Metastases

Sharma¹,

Tran²,

et al. 2006

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Malignant melanoma has a high propensity for metastatic spread, making it the most deadly form of skin cancer. B-RAF has been identified as the most mutated gene in these invasive cells and therefore an attractive therapeutic target. However, for uncertain reasons, chemotherapy inhibiting B-Raf has not been clinically effective. This has raised questions whether this pathway is important in melanoma metastasis or whether targeting a protein other than B-Raf in the signaling cascade could more effectively inhibit this pathway to reduce lung metastases. Here, we investigated the role played by V600E B-Raf in melanoma metastasis and showed that targeting this signaling cascade significantly reduces lung metastases. Small interfering RNA (siRNA)-mediated inhibition was used in mice to reduce expression (activity) of each member of the signaling cascade and effects on metastasis development were measured. Targeting any member of the signaling cascade reduced metastasis but inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (Mek) 1 and Mek 2 almost completely prevented lung tumor development. Mechanistically, metastatic inhibition was mediated through reduction of melanoma cell extravasation through the endothelium and decreased proliferative capacity. Targeting B-Raf with the pharmacologic inhibitor BAY 43-9006, which was found ineffective in clinical trials and seems to act primarily as an angiogenesis inhibitor, did not decrease metastasis, whereas inhibition of Mek using U0126 decreased cellular proliferative capacity, thereby effectively reducing number and size of lung metastases. In summary, this study provides a mechanistic basis for targeting Mek and not B-Raf in the mutant V600E B-Raf signaling cascade to inhibit melanoma metastases. (Cancer Res 2006; 66(16): 8200-9)

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The Biophysics of Cancer: Emerging Insights from Micro‐ and Nanoscale Tools

Beshay

Cortes-Medina

Menyhert

et al. 2021

Advanced NanoBiomed Research

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Cancer is a complex and dynamic disease that is aberrant both biologically and physically. There is growing appreciation that physical abnormalities with both cancer cells and their microenvironment that span multiple length scales are important drivers for cancer growth and metastasis. The scope of this review is to highlight the key advancements in micro‐ and nanoscale tools for delineating the cause and consequences of the aberrant physical properties of tumors. Herein, the following three important physical aspects of cancer are focused: 1) solid mechanical properties, 2) fluid mechanical properties, and 3) mechanical alterations to cancer cells. Beyond posing physical barriers to the delivery of cancer therapeutics, these properties are also known to influence numerous biological processes, including cancer cell invasion and migration leading to metastasis, and response and resistance to therapy. There is a comment on how micro‐ and nanoscale tools have transformed the fundamental understanding of the physical dynamics of cancer progression and their potential for bridging toward future applications at the interface of oncology and physical sciences.

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Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion

Cited by 62 publications

References 40 publications

Targeting Mutant (V600E)B-Rafin Melanoma Interrupts Immunoediting of Leukocyte Functions and Melanoma Extravasation

Targeting Mutant (V600E)B-Rafin Melanoma Interrupts Immunoediting of Leukocyte Functions and Melanoma Extravasation

Targeting Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Kinase in the Mutant (V600E) B-Raf Signaling Cascade Effectively Inhibits Melanoma Lung Metastases

The Biophysics of Cancer: Emerging Insights from Micro‐ and Nanoscale Tools

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