Robin Scorpio-Drake (Kimberly McCullough)
Two experimental replicates were conducted. Generalized linear models were used to assess the relationship between treatments and experimental response [ 22 ]. The number of invadopodia per cell and the frequency of invadopodia-positive cells were modeled by binomial logit link and Poisson log link generalized linear models, respectively. Treatment differences for single continuous responses such as cell displacement and cAMP accumulation were analyzed by analysis of variance.
For the fitted models, we report estimated regression coefficients quantifying the relationship between the response and treatments, and the corresponding p values for testing the null hypothesis of no treatment effect. Statistical analysis was carried out in the R computing environment [ 24 ]. Generalized linear models were fitted using the routine glm while multiple comparisons used the routine glht in the package multicomp [ 25 ].
Error bars: standard error of the mean SEM. ND: not detected.
Treatment with isoproterenol led to an increase in the frequency of invadopodia-positive cells, with a maximum increase of 2. In addition to increasing the frequency of invadopodia-positive cells in the population Fig. Representative images are shown. Error bars: SEM.
Formation of invadopodia requires adhesion proteins that may be sequestered from focal adhesions [ 6 ]. Isoproterenol resulted in a concentration-dependent decrease in adhesion length and decreased number of focal adhesions per cell Fig. Loss of focal adhesion-associated proteins has been linked to a decreased frequency of focal adhesions and reduced capacity for cell migration on two-dimensional surfaces [ 29 ].
Consistent with the change in focal adhesions having a functional effect on cell movement, isoproterenol decreased the migration of cancer cells on a two-dimensional fibronectin surface Fig. Square brackets in inset identify focal adhesions. Red cross marks the location of the cell at the commencement of treatment.
Time in hours is indicated. To investigate this, MDA-MB breast cancer cells were embedded in collagen matrix and cell locomotion was tracked over time. Under control conditions, cells remained rounded with little displacement from the position of origin Fig. Treatment with PP2 alone did not significantly change the frequency of invadopodia compared to treatment with vehicle. Treatment with PP2 also blocked the effect of formoterol on invasion of cells in three-dimensional collagen matrix Fig.
For example, norepinephrine was shown to protect cancer cells from anoikis by activating and relocalizing focal adhesion kinase [ 34 ]. Mice were implanted with luciferase-tagged MDA-MB cells into the left fourth mammary fat pad and spontaneous metastasis was tracked by bioluminescence imaging using 1-second exposure to detect signals from primary tumors and second exposure to detect signals from metastases Fig. Treatment with formoterol during tumor development accelerated the formation of metastasis Fig.
In contrast to tumors from vehicle-treated mice, which demonstrated minimal invasion of cells into the surrounding extracellular matrix over the 8-day imaging period, tumors from mice treated with formoterol had rapid invasion of tumor cells into the surrounding matrix Fig. Luciferase-tagged tumor cells were injected into the fourth mammary fat pad PT and spontaneous metastases to the lymph node and lung Met were detected by optical bioluminescence imaging.
Black bar separates images taken with two different exposures. Metastasis is a highly inefficient process and requires successful completion of a series of inter-connected steps including dissemination from the primary tumor, survival in circulation, extravasation, and colonization at distant sites [ 37 — 39 ]. Failure at any stage of metastasis will result in failure of the entire process [ 40 ]. These findings suggest that blocking tumor cell responsiveness to stress signaling may protect against tumor cell invasion and metastasis.
Breast cancer metastasis: markers and models. Nat Rev Cancer.
- canoscan lide 100 mac 10.7?
- Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1.
- New Research In!
Actin dynamics at sites of extracellular matrix degradation. Eur J Cell Biol. Local degradation of fibronectin at sites of expression of the transforming gene product pp60src. Chen WT. Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells. J Exp Zool.
CAS promotes invasiveness of Src-transformed cells. FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion.
The Journal of cell biology. Microenvironmental regulation of tumor progression and metastasis. Nat Med. The beta2-adrenergic receptor and Her2 comprise a positive feedback loop in human breast cancer cells. Breast Cancer Res Treat. Alpha- and beta-adrenergic receptor AR protein expression is associated with poor clinical outcome in breast cancer: an immunohistochemical study. Kobilka B.
Adrenergic receptors as models for G protein-coupled receptors. Annu Rev Neurosci. Neuroendocrine modulation of signal transducer and activator of transcription-3 in ovarian cancer. Cancer Res. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer research.
β2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion
Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain, behavior, and immunity. Src activation by beta-adrenoreceptors is a key switch for tumour metastasis. Nature Communications.
FOXC1, a target of polycomb, inhibits metastasis of breast cancer cells. PEGylation of interferon alpha2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases.
Stay up to date
J Control Release. Genomic analysis of a spontaneous model of breast cancer metastasis to bone reveals a role for the extracellular matrix. Mol Cancer Res. Automated analysis of invadopodia dynamics in live cells. High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS One. An Introduction to Generalized Linear Models. CRC Press; Hsu J.
- RESEARCH REPORT - Peter MacCallum Cancer Centre.
- mac whirl lip liner with velvet teddy.
- remove yahoo toolbar from firefox mac.
- gameboy color roms for mac os x.
- speed test for mac os x.
- Robin Boyd (architect).
- Prof. Robin Anderson;
Multiple Comparisons: Theory and Methods. USA: CA; Multiple Comparisons using R. Effects of chronic rosiglitazone therapy on gene expression in human adipose tissue in vivo in patients with type 2 diabetes. J Clin Endocrinol Metab. Cell Metab. Beta-adrenoceptor signaling and its control of cell replication in MDA-MB human breast cancer cells. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover.
J Cell Sci.
Epinephrine inhibits invasion of oral squamous carcinoma cells by modulating intracellular cAMP. Cancer Lett. J Invest Dermatol. Pharm Biol —8. Norepinephrine inhibits the migratory activity of pancreatic cancer cells. Exp Cell Res. Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis.