β1 integrin is required for anchorage-independent growth and invasion of tumor cells in a context dependent manner

Schooley, Allana; Andrews, Natalie M.; Zhao, Huijun; Addison, Christina L.

doi:10.1016/j.canlet.2011.10.032

Cited by 16 publications

(14 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growing evidence supports a central role for integrins in controlling growth and survival under anchorage-independent conditions, a property critical for hematogeneous metastasis. For example, integrin β1 promotes anchorage-independent growth in prostate [58] and breast cancer cells by activating a FAK/PAK/MAPK signaling cascade [59], while integrin β3 interacts with c-Src independently of FAK signaling to drive increased anchorage-independence and lymph node metastasis in pancreatic and breast cancer tumor models [32]. The paradigm of integrin-mediated anchorage-independent growth may be explained in part by the ability of specific integrins to form cell surface clusters in response to growth factors or oncogenes and drive downstream signaling [13, 60].…”

Section: Critical Roles For Integrins During the Metastatic Cascadementioning

confidence: 99%

Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance

Seguin

Desgrosellier

Weis

et al. 2015

Trends in Cell Biology

595

555

View full text Add to dashboard Cite

Summary Interactions between cancer cells and their surroundings can trigger essential signaling cues that determine cell fate and influence the evolution of the malignant phenotype. As the primary receptors involved in cell-matrix adhesion, integrins present on the surface of tumor and stromal cells have a profound impact on the ability to survive in specific locations, but in some cases these receptors can also function in the absence of ligand binding to promote stemness and survival in the presence of environmental and therapeutic stresses. Understanding how integrin expression and function is regulated in this context will enable the development of new therapeutic approaches to sensitize tumors to therapy and suppress their metastatic phenotype.

show abstract

Section: Critical Roles For Integrins During the Metastatic Cascadementioning

confidence: 99%

Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance

Seguin

Desgrosellier

Weis

et al. 2015

Trends in Cell Biology

595

555

View full text Add to dashboard Cite

show abstract

“…To capture all of these levels of regulation, it would be advantageous to measure MMP activity at the site of action when it is occurring within the sample of interest. Additionally, mounting evidence indicates that microenvironmental cues (e.g., dimensionality, matrix stiffness, adhesion ligand presentation) also regulate MMP activity (10)(11)(12)(13)(14), so there is an increasing need for three-dimensional (3D) in vitro culture systems in which MMP activity can be measured quickly and simply to bridge the gap between traditional 2D cell culture and in vivo models. Three-dimensional culture systems are quite relevant to evaluate how drug candidates affect cellular MMP activity, because they provide a more physiologically relevant context, which necessitates breakdown of the surrounding matrix to allow migration and invasion in a dense ECM-like environment.…”

mentioning

confidence: 99%

Multifunctional bioscaffolds for 3D culture of melanoma cells reveal increased MMP activity and migration with BRAF kinase inhibition

Leight

Tokuda

Jones

et al. 2015

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

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are important for many different types of cancer-related processes, including metastasis. Understanding the functional impact of changes in MMP activity during cancer treatment is an important facet not typically evaluated as part of preclinical research. With MMP activity being a critical component of the metastatic cascade, we designed a 3D hydrogel system to probe whether pharmacological inhibition affected human melanoma cell proteolytic activity; metastatic melanoma is a highly aggressive and drug-resistant form of skin cancer. The relationship between MMP activity and drug treatment is unknown, and therefore we used an in situ fluorogenic MMP sensor peptide to determine how drug treatment affects melanoma cell MMP activity in three dimensions. We encapsulated melanoma cells from varying stages of progression within PEG-based hydrogels to examine the relationship between drug treatment and MMP activity. From these results, a metastatic melanoma cell line (A375) and two inhibitors that inhibit RAF (PLX4032 and sorafenib) were studied further to determine whether changes in MMP activity led to a functional change in cell behavior. A375 cells exhibited increased MMP activity despite an overall decrease in metabolic activity with PLX4032 treatment. The changes in proteolytic activity correlated with increased cell elongation and increased single-cell migration. In contrast, sorafenib did not alter MMP activity or cell motility, showing that the changes induced by PLX4032 were not a universal response to small-molecule inhibition. Therefore, we argue the importance of studying MMP activity with drug treatment and its possible implications for unwanted side effects.hydrogel | cancer | matrix metalloproteinase | cell motility | BRAF/MEK P roteolytic cleavage of the tumor microenvironment is an important mediator of cancer metastasis, which is the primary cause of mortality in cancer patients. Remodeling of the local environment involves a complex balance of cellularly secreted enzymes that promote and inhibit matrix degradation (reviewed in ref. 1). As part of this process, the matrix metalloproteinase (MMP) family of zinc-dependent enzymes plays a key role in this remodeling by degrading extracellular matrix (ECM) proteins, which promotes tumor cell invasion and colonization of distant metastatic sites, stimulates blood vessel infiltration, and releases numerous growth factors (2-6). MMP expression is elevated in nearly all solid tumors, including breast, colon, pancreas, and melanoma, and increased expression is often correlated with decreased survival (7). Additionally, targeted overexpression of MMP-3, -7, or -14 in vivo results in increased mammary carcinogenesis (8), and several knockout mouse models have decreased tumor incidence, angiogenesis, and metastasis (9).Although clearly important during cancer progression, MMP activity is not routinely evaluated during in vitro preclinical screening for potential cancer therapeutics. This is due partly to the many layers of regulat...

show abstract

“…39 We further observed that inhibition of fibronectin-β1 integrin interactions following use of neutralizing antibodies to fibronectin resulted in a similar inhibition of anchorage-independent growth, suggesting that this ECM-integrin interaction plays an important role in this process. Interestingly, we saw no difference in the growth or survival of β1-depleted tumor cells [including prostate, 39 lung and neuroblastoma tumor lines (unpublished personal findings)], following growth in 2D culture conditions, possibly as a result of other β-subunit containing integrins compensating for lack of β1 under these conditions Alternatively, the fact that 2D culture promotes clustering of integrins and their signaling partners at sites of focal adhesions may result in cell signaling that significantly differs than that which occurs in 3D growth.…”

Section: B1 Integrin Regulates Tumorigenesis In 3d Contextsmentioning

confidence: 54%

“…[49][50][51] In addition to modulation of anchorage-independent growth, we also identified an important role for β1 integrin in regulating tumor cell invasion through 3D ECM gels. 39 We elucidated a putative mechanism whereby β1 integrin-depleted prostate tumor cells expressed decreased levels of MMP-9 with concomitant increased expression of TIMP2 as compared with control cells following culture on fibronectin. This suggests that β1-containing integrins, likely a5β1 which is one of the primary fibronectin receptors in tumor cells, are responsible for the upregulation of MMP-9.…”

Section: B1 Integrin Regulates Tumor Cell Invasionmentioning

confidence: 99%

β1 integrin

Howe

Addison

2012

Cell Adhesion & Migration

Self Cite

View full text Add to dashboard Cite

β1 integrin is required for anchorage-independent growth and invasion of tumor cells in a context dependent manner

Cited by 16 publications

References 76 publications

Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance

Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance

Multifunctional bioscaffolds for 3D culture of melanoma cells reveal increased MMP activity and migration with BRAF kinase inhibition

β1 integrin

Contact Info

Product

Resources

About