Regulatory expression of MMP‐8/MMP‐9 and inhibition of proliferation, migration and invasion in human lung cancer A549 cells in the presence of HGF variants

Ramanujum, Rakesh; Lin, Yaling; Liu, Jong-Kang; He, Songqing

doi:10.1016/j.kjms.2013.01.011

Cited by 16 publications

(21 citation statements)

References 52 publications

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“…In this paper, we compare three types of A549 cells in the invasion stacks: i) A549, which are basal epithelial cells of a human alveolar adenocarcinoma (34); ii) A549-HGF, which are A549 cells engineered to express hepatocyte growth factor (HGF) constitutively (35,36); and iii) A549-HGF-M, which is a subclone of the A549-HGF cells derived from a lung metastasis in a xenograft tumor grown in an immune-compromised mouse.…”

Section: Resultsmentioning

confidence: 99%

A paper-based invasion assay: Assessing chemotaxis of cancer cells in gradients of oxygen

et al. 2015

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This work describes a 3D, paper-based assay that can isolate subpopulations of cells based on their invasiveness (i.e., distance migrated in a hydrogel) in a gradient of concentration of oxygen (O 2 ). Layers of paper impregnated with a cell-compatible hydrogel are stacked and placed in a plastic holder to form the invasion assay. Stacking the layers of paper assembles them into 3D tissue-like constructs of defined thickness and composition. The plastic holder ensures the layers of paper are in conformal contact; this geometry allows the cells to migrate between adjacent layers through the embedded hydrogel. In most assays, the stack comprises a single layer of paper containing mammalian cells suspended in a hydrogel, sandwiched between multiple layers of paper containing only hydrogel (into which the cells migrate). Cells in the stack consume and produce small molecules; these molecules diffuse throughout the stack to generate gradients both in the stack, and between the stack and the bulk culture medium. Placing the cell-containing layer in different positions of the stack, or modifying the permeability of the holder to oxygen or proteins, alters the profile of the gradients within the stack. Physically separating the layers after culture isolates subpopulations of cells that migrated different distances, and enables their subsequent analysis or culture. Using this system, three independent cell lines derived from A549 cancer cells are shown to produce distinguishable migration behavior in a gradient of oxygen. This result is the first experimental demonstration that oxygen acts as a chemoattractant for cancer cells. Page 3 of 35 Significance StatementThe invasion of cancerous cells from a tumor into surrounding tissues is one contribution to metastasis-a major contributor to death for patients with cancer. There is a strong link between the directed invasion of cancer cells and the gradients of molecules formed in the microenvironment of the tumor. Using a paper-based invasion assay, this work demonstrates that oxygen-a nutrient known to induce significant behavioral changes to cells within a tumor in a concentration-dependent manner-can also act as a chemoattractant, resulting in the migration of cancer cells towards higher concentrations of oxygen. This finding, and the invasion assay described, could lead to a better understanding of oxygen-based chemotaxis in cancer, and ultimately new strategies for managing metastasis.

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Section: Resultsmentioning

confidence: 99%

A paper-based invasion assay: Assessing chemotaxis of cancer cells in gradients of oxygen

et al. 2015

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“…This effect damages the physical barrier around tumor cells, increasing the tumor biological activity by degrading the matrix components, which allows the tumor to escape from the immune system. The changes of the ECM lead to an increase of tumor angiogenesis, leading to further pituitary adenoma proliferation and invasive growth (Ramanujum et al, 2013;Pereira et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Regulating effect of MMP-9 and TIMP-1 in pituitary adenoma invasion

Mao

Guo

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Pituitary adenomas can cause endocrine disorder and organ damage, with some aggressive ones leading to a high postoperative recurrence rate. The occurrence and development of these type of tumors is closely related with matrix metalloproteinases (MMPs) and endogenous specific tissue inhibitor of MMPs (TIMPs). In this study, the relationship between pituitary adenoma invasion and the changes in MMP-8 and TIMP-1 expressions is analyzed. Specimens from sixty patients with pituitary adenoma were collected in our hospital after surgery, including thirty cases of invasive pituitary adenomas and thirty cases of noninvasive pituitary adenomas. Western blotting and real-time PCR were used to detect MMP-8/TIMP-1 protein and mRNA levels, respectively, in the two types of pituitary adenomas, while ELISA was used to detect both compounds' levels in the patient's serum. Compared with noninvasive pituitary adenomas, MMP- 8 was significantly overexpressed in invasive pituitary adenomas, while TIMP-1 was obviously lower (P < 0.05 for both). Moreover, MMP-8 mRNA expression in invasive pituitary adenomas was significantly higher than in noninvasive pituitary adenomas, while TIMP-1 mRNA expression was markedly lower (P < 0.05 for both). Finally, MMP-8 expression in the serum is upregulated in patients with invasive pituitary adenomas relative to the noninvasive ones, and the expression of TIMP-1 significantly reduced (P < 0.05 for both). These results show that increased MMP-8 and decreased TIMP-1 expressions are closely related to the invasive pituitary adenoma, and can be helpful for the evaluation.

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“…The HGF/MET axis is believed to contribute significantly to proliferation, metastasis, extracellular matrix remodeling, tumor cell survival, and angiogenesis associated with tumors [176,177,178]. MET , originally identified as a proto-oncogene [179,180], was found to be up-regulated in a variety of cancers, inducing its constitutive expression [181,182,183,184,185,186].…”

Section: Biological Functions Of Hgf and Its Isoformsmentioning

confidence: 99%

“…For instance, both NK1 and NK2 inhibited the proliferation and motility of A549 lung cancer cell line in vitro [176]. In these same cells, both NK1 and NK2 altered the expression of matrix metaloproteinases, suggesting that the mechanism for the reduction of cellular motility in part lay in altered interactions with the extracellular matrix and increasing the adhesion capacity of the cells [176].…”

Section: Biological Functions Of Hgf and Its Isoformsmentioning

confidence: 99%

Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling

2014

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Hepatocyte growth factor (HGF), also known as scatter factor (SF), is a pleotropic factor required for normal organ development during embryogenesis. In the adult, basal expression of HGF maintains tissue homeostasis and is up-regulated in response to tissue injury. HGF expression is necessary for the proliferation, migration, and survival of epithelial and endothelial cells involved in tissue repair in a variety of organs, including heart, lung, kidney, liver, brain, and skin. The administration of full length HGF, either as a protein or using exogenous expression methodologies, increases tissue repair in animal models of tissue injury and increases angiogenesis. Full length HGF is comprised of an N-terminal hairpin turn, four kringle domains, and a serine protease-like domain. Several naturally occurring alternatively spliced isoforms of HGF were also identified. The NK1 variant contains the N-terminal hairpin and the first kringle domain, and the NK2 variant extends through the second kringle domain. These alternatively spliced forms of HGF activate the same receptor, MET, but they differ from the full length protein in their cellular activities and their biological functions. Here, we review the species-specific expression of the HGF isoforms, their regulation, the signal transduction pathways they activate, and their biological activities.

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Regulatory expression of MMP‐8/MMP‐9 and inhibition of proliferation, migration and invasion in human lung cancer A549 cells in the presence of HGF variants

Cited by 16 publications

References 52 publications

A paper-based invasion assay: Assessing chemotaxis of cancer cells in gradients of oxygen

A paper-based invasion assay: Assessing chemotaxis of cancer cells in gradients of oxygen

Regulating effect of MMP-9 and TIMP-1 in pituitary adenoma invasion

Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling

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Regulatory expression of MMP‐8/MMP‐9 and inhibition of proliferation, migration and invasion in human lung cancer A549 cells in the presence of HGF variants

Cited by 16 publications

References 52 publications

A paper-based invasion assay: Assessing chemotaxis of cancer cells in gradients of oxygen

A paper-based invasion assay: Assessing chemotaxis of cancer cells in gradients of oxygen

Regulating effect of MMP-9 and TIMP-1 in pi­tuitary adenoma invasion

Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling

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Regulating effect of MMP-9 and TIMP-1 in pituitary adenoma invasion