Cancer metastasis: A product of tumor-host interactions

Sugarbaker, Everett V.

doi:10.1016/s0147-0272(79)80008-2

Cited by 131 publications

(64 citation statements)

References 87 publications

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“…This increased adhesion is accompanied by a variety of cytoskeletal rearrangements typical of increased adhesion and cell motility. 3 These observations are similar to those seen in other cell types (e.g. Refs.…”

Section: Resultssupporting

confidence: 90%

“…Arachidonic acid-induced adhesion is accompanied by a variety of cytoskeletal rearrangements typical of increased adhesion and cell motility. 3 We show here that RhoA and its regulator p115RhoGEF are required for arachidonic acid-induced changes in cell morphology and cytoskeleton. These data indicate that arachidonic acid-induced Rho signaling is critical both for cell adhesion to collagen IV and for the regulation of actin filament formation.…”

Section: Discussionmentioning

confidence: 66%

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Arachidonic Acid Stimulates Cell Adhesion through a Novel p38 MAPK-RhoA Signaling Pathway That Involves Heat Shock Protein 27

Garcia

Ray

Lackford

et al. 2009

Journal of Biological Chemistry

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Rho GTPases are critical components of cellular signal transduction pathways. Both hyperactivity and overexpression of these proteins have been observed in human cancers and have been implicated as important factors in metastasis. We previously showed that dietary n-6 fatty acids increase cancer cell adhesion to extracellular matrix proteins, such as type IV collagen. Here we report that in MDA-MB-435 human melanoma cells, arachidonic acid activates RhoA, and inhibition of RhoA signaling with either C3 exoenzyme or dominant negative Rho blocked arachidonic acid-induced cell adhesion. Inhibition of the Rho kinase (ROCK) with either small molecule inhibitors or ROCK II-specific small interfering RNA (siRNA) blocked the fatty acid-induced adhesion. However, unlike other systems, inhibition of ROCK did not block the activation of p38 mitogenactivated protein kinase (MAPK); instead, Rho activation depended on p38 MAPK activity and the presence of heat shock protein 27 (HSP27), which is phosphorylated downstream of p38 after arachidonic acid treatment. HSP27 associated with p115RhoGEF in fatty acid-treated cells, and this association was blocked when p38 was inhibited. Furthermore, siRNA knockdown of HSP27 blocked the fatty acid-stimulated Rho activity. Expression of dominant negative p115-RhoGEF or p115RhoGEF-specific siRNA inhibited both RhoA activation and adhesion on type IV collagen, whereas a constitutively active p115RhoGEF restored the arachidonic acid stimulation in cells in which the p38 MAPK had been inhibited. These data suggest that n-6 dietary fatty acids stimulate a set of interactions that regulates cell adhesion through RhoA and ROCK II via a p38 MAPK-dependent association of HSP27 and p115RhoGEF.The ability of tumor cells to metastasize to secondary sites is a hallmark of neoplastic disease. Unfortunately, this propensity to spread is the primary cause of morbidity and death in cancer patients (1). Metastasis is clearly a highly regulated, multistep process that occurs in a spatiotemporal manner (2-4). To escape the restrictive compartment boundaries characteristic of adult tissue, separate intravasation and extravasation steps requiring alterations in co-adhesion, adhesion, invasion, and migration must occur. Execution of these biological processes, involving multiple proteins and cellular organelles, require highly coordinated cell signaling mechanisms.The Rho family of small GTPases regulates many facets of cytoskeletal rearrangements that facilitate cell attachment and migration (5-7). Rho GTPases act as molecular switches by changing from an inactive GDP-bound conformation to an active GTPbound conformation, thereby regulating a signaling pathway. These proteins are directly regulated by Rho guanine nucleotide exchange factors (GEFs), 2 Rho GTPase activating proteins, and Rho GDP-dissociation inhibitors (8 -12). RhoGEFs bind to the GTPase to catalyze the dissociation of GDP, allowing the binding of GTP and thereby promoting Rho activation (8). The RGS (regulators of G protein signaling) domain-c...

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Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 66%

Arachidonic Acid Stimulates Cell Adhesion through a Novel p38 MAPK-RhoA Signaling Pathway That Involves Heat Shock Protein 27

Garcia

Ray

Lackford

et al. 2009

Journal of Biological Chemistry

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“…In our tumour models there was no metastasis to the liver and direct correlation between rise in serum bound NANA and metastasis. Recently, a report by Huggins et al (1980) (Sugarbaker, 1979). Tumour cells have been shown to contain plasminogen activator which is capable of activating the blood proenzyme plasminogen to plasmin (Ramshaw et al, 1982).…”

Section: Resultsmentioning

confidence: 99%

“…Serum specimens Rats were bled from the tail vein prior to tumour cell injection (pre-bleed sera) and periodically thereafter (Hoon et al, 1983 (Silver et al, 1979), compared to the colorimetric procedures (Tuppy & Gottschalk, 1972). The NANA was hydrolyzed from its bound form by acid treatment as follows: the sample was diluted 1:20 (v/v) with 0.1 M sulphuric acid, while the culture medium sample was diluted 1:10 with 1 M sulphuric acid.…”

Section: Animals and Tumour Cell Linesmentioning

confidence: 99%

Analysis of mammary tumour cell metastasis and release of bound n-acetylneuraminic acid

Hoon¹,

Ng²,

Ramshaw³

1985

Br J Cancer

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Summary A tumour model consisting of the highly metastatic mammary 13762 parental line, the nonmetastatic and 6-thioguanine-resistant (TgR) variant line, and two TgR revertant lines (TgRrev, TgRrevM) that were occasionally metastatic, were used to determine whether the relase of N-acetylneuraminic acid (NANA) was related to tumour metastasis. For comparative purposes, the occasionally metastatic R3230AC and the nonmetastatic DMBA8 tumour lines were studied. The NANA was considered to be in bound form, because acid hydrolysis was required to release it for high-pressure liquid chromatographic analyses. Sera of animals bearing the 13762 and R3230AC tumours had high levels of bound NANA. No differences were found in serum NANA levels in animals bearing metastatic or non-metastatic R3230AC tumours. Low levels of bound NANA were found in animals bearing the other tumour lines regardless of whether metastasis occurred or not. The experiments in vitro substantiated the in vivo findings. The phenotypic expression of bound NANA shedding did not correlate well with metastatic potential of the mammary tumour line. Our analyses suggest that this phenotypic marker cannot be used as a reliable indicator of metastasis.

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“…Fidler et al ( I ) and Sugarbaker (2) reported that the formation of metastatic lesion passes through a series of complicated processes such as detachment of cancer cells, invasion of surrounding tissue, invasion of lymph and blood vessels, circulation, arrest, extravasation, and growth. Of these processes, detachment and infiltration of cancer cells are very important steps, and both mechanical (3) and chemical factors are considered to be involved.…”

mentioning

confidence: 99%