Article

Two sides to cilia in cancer.

Rune Toftgård is at the Karolinska Institutet Center for Biosciences, Department of Biosciences and Nutrition, NOVUM, Huddinge, Sweden.
Nature medicine (Impact Factor: 28.05). 10/2009; 15(9):994-6. DOI: 10.1038/nm0909-994
Source: PubMed

ABSTRACT The primary cilium can keep cancer at bay, or it can instigate tumor development, according to studies in mice (pages 1055–1061 and 1062–1065). The outcome depends on the nature of the initiating event, which involves signaling through the Hedgehog pathway.

0 Followers
 · 
80 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As cancer progresses, a dynamic microenvironment develops that creates and responds to cellular and biophysical cues. Increased intratumoral pressure and corresponding increases in interstitial flow from the tumor bulk to the healthy stroma is an observational hallmark of progressing cancers. Until recently, the role of interstitial flow was thought to be mostly passive in the transport and dissemination of cancer cells to metastatic sites. With research spanning the past decade, we have seen that interstitial flow has a promigratory effect on cancer cell invasion in multiple cancer types. This invasion is one mechanism by which cancers can resist therapeutics and recur, but the role of interstitial flow in cancer therapy is limited to the understanding of transport of therapeutics. Here we outline the current understanding of the role of interstitial flow in cancer and the tumor microenvironment through cancer progression and therapy. We also discuss the current role of fluid flow in the treatment of cancer, including drug transport and therapeutic strategies. By stating the current understanding of interstitial flow in cancer progression, we can begin exploring its role in therapeutic failure and treatment resistance.
    Cancer Management and Research 08/2014; 6:317-28. DOI:10.2147/CMAR.S65444
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dysfunctional cilia underlie a broad range of cellular and tissue phenotypes and can eventually result in the development of ciliopathies: pathologically diverse diseases that range from clinically mild to highly complex and severe multi-organ failure syndromes incompatible with neonatal life. Given that virtually all cells of the human body have the capacity to generate cilia, it is likely that clinical manifestations attributed to ciliary dysfunction will increase in the years to come. Disputed but nevertheless enigmatic is the notion that at least a subset of tumor phenotypes fit within the ciliopathy disease spectrum and that cilia loss may be required for tumor progression. Contending for the centrosome renders ciliation and cell division mutually exclusive; a regulated tipping of balance promotes either process. The mechanisms involved, however, are complex. If the hypothesis that tumorigenesis results from dysfunctional cilia is true, then why do the classic ciliopathies only show limited hyperplasia at best? Although disassembly of the cilium is a prerequisite for cell proliferation, it does not intrinsically drive tumorigenesis per se. Alternatively, we will explore the emerging evidence suggesting that some tumors depend on ciliary signaling. After reviewing the structure, genesis and signaling of cilia, the various ciliopathy syndromes and their genetics, we discuss the current debate of tumorigenesis as a ciliopathy spectrum defect, and describe recent advances in this fascinating field.
    04/2013; 2(1):6. DOI:10.1186/2046-2530-2-6
  • [Show abstract] [Hide abstract]
    ABSTRACT: The etiology of benign prostatic hyperplasia [BPH] in elderly men has intrigued anatomists, pathologists and scientists for centuries. Studies of morbid anatomy, clinical observations and contemporary cellular biology have contributed to an evolving interpretation of the causality of the disease. Insights into the detailed microanatomy and ductal architecture of the prostate during stages of fetal and early postnatal development suggest that mechanisms involved in the early growth period become aberrantly expressed in elderly men. Age, hormones and epithelial-mesenchymal interactions are all contributing factors to the pathogenesis of BPH. Control of the microenvironment in normal and abnormal growth is a multifactorial process. Susceptibility to the disease may include clinical comorbid diseases, region-specific changes in cell-cell interactions and a variety of signaling pathways including a novel hypothesis regarding the role of the primary cilium as a regulator of signal transduction mechanisms. Recent work in animal models has shown that there are region-specific differences within the prostate that may be significant because of the dynamic and intricate interplay between the epithelium and mesenchyme. Because of the focal nature of BPH a closer examination of normal morphogenesis patterns, which defines the gland's architecture, may facilitate a detailed understanding of the atypical growth patterns.
    Differentiation 11/2011; 82(4-5):173-83. DOI:10.1016/j.diff.2011.08.002 · 2.84 Impact Factor

Preview

Download
1 Download
Available from