Successful completion of meiosis in vertebrate oocytes requires the localization and maintenance of the meiotic spindle at the cell cortex. Arp2/3-nucleated actin filaments are now shown to flow away from the cortex overlying the spindle, resulting in cytoplasmic streaming, which maintains the spindle in its asymmetric position.
Melanoma cells can invade surrounding tissue
As we said in a press release last night, our scientists at the Beatson Institute in Scotland have made an interesting discovery about how skin develops – a discovery that also helps us understand melanoma a bit better too.
The researchers were looking at how immature skin pigment cells, called melanoblasts, move around and find their correct location in the developing skin in mice, before maturing into melanocytes – pigment cells that can develop into melanoma when damaged (for example by UV light).
Melanoblasts, scientists had previosuly discovered, move around by extending long ‘legs’ into the surrounding tissue and literally hauling themselves into the correct position.
The Glasgow team, led by Professor Laura Machesky, found that a gene known as Rac1 was a key player in this process. They also discovered that interfering with Rac1 stopped the melanoblasts from moving around, and prevented mice’s skin from becoming properly pigmented. They’ve published their findings in the journal Developmental Cell.
But how is this relevant to cancer? We’ve tried to sum things up in a handy graphic, which you can see below:
Click to enlarge
Although every cell in our body contains the full complement of 30,000 genes, only a subset are switched on in a given cell at a given point in its life-cycle. Consequently, Rac1 is only switched on at certain times – in this case during melanoblasts’ development.
But cancer cells, with their highly disordered and damaged DNA, seem to switch many of these developmental genes back on. In fact, cancer cells seem to regress back to their ‘childhood’ and start misbehaving.
And there’s a fair amount of evidence that Rac1 is indeed switched on in melanoma cells.
Given that researchers now know that Rac1 is a key player in how early pigment cells move around in the developing skin in mice, this suggests that the gene could be doing a similar job in melanoma cells in humans. More work is needed to find out if this holds true, but if it does then interfering with Rac1 – or other proteins it works with – in cancer cells could be a way to stop melanoma spreading (provided, of course, that this doesn’t interfere with the body’s day-to-day functioning).
It’s a small step, but science is a series of small steps that often take us in surprising new directions. We’ll be following the Beatson team’s future work with interest.
Henry
Image via Wikimedia Commons
Reference:
Li et al: Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod-driven motility and cell cycle progression. Developmental Cell (2011)feedproxy.google.com
Gene therapy delivered directly to a particularly stubborn type of breast cancer cell causes the cells to self-destruct, lowers chance of recurrence and helps increase the effectiveness of some types of chemotherapy. (2011-09-13) www.brightsurf.com
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Researchers at The University of Texas M.D. Anderson Cancer Center have found that gene therapy if delivered directly to a particular type of breast cancer cell causes the cell to self-destruct, there feeds.bignewsnetwork.com
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Ranpirnase Interferes with NF-?B Pathway and MMP9 Activity, Inhibiting Malignant Mesothelioma Cell Invasiveness and Xenograft Growth.
Genes Cancer. 2011 May;2(5):576-84
Authors: Nasu M, Carbone M, Gaudino G, Ly BH, Bertino P, Shimizu D, Morris P, Pass HI, Yang H
Abstract
The ribonuclease ranpirnase (Onconase) has been used empirically to treat malignant mesothelioma (MM) patients, and some of them had prolonged survivals. The aim of this study was to investigate the mechanisms of the therapeutic function of ranpirnase in MM cells. The effects of ranpirnase were studied in vivo and in vitro on 2 MM cell lines (epithelioid REN and sarcomatoid PPM-Mill). We found that ranpirnase was able to inhibit NF-?B nuclear translocation, evaluated by cell fractionation and immunoblotting as well as by immunofluorescence. Also, MMP9 secretion by MM cells was decreased by ranpirnase treatment, as assessed by the reduction of metalloproteinase activity, evaluated by zymography on culture-conditioned media. Ranpirnase induced apoptosis of MM cells in vitro and in vivo, causing a powerful inhibition of MM tumor growth in SCID xenografts, determined by In Vivo Imaging System (IVIS) of tumor cells engineered by lentiviral transduction of the luciferase gene. Finally, mice treated with ranpirnase showed a significantly prolonged survival. Our data provide a mechanistic rationale to explain the beneficial antitumor activity observed in some patients treated with ranpirnase and demonstrate that ranpirnase interferes with the NF-?B pathway, thus influencing MM tumor cell invasiveness and survival. It is hoped that this information will also facilitate the identification of those patients who are more likely to benefit from this drug and will also open a new frontier for the use of this drug in tumor types other than MM.
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