Polyps as biomarkers for colorectal neoplasia

Tobi, Martin

doi:10.2741/a431

Cited by 11 publications

(11 citation statements)

References 27 publications

(36 reference statements)

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“…Curiously, Paneth cell differentiation is also disrupted on complete ablation of Lkb1 in intestinal epithelium before a larger disruption of epithelial architecture and lethality. 49 Contrary to current understanding, 6,34,50 this study demonstrated that Peutz-Jeghers polyps do not contain all epithelial cell types and lineages native to their site of occurrence. Some epithelial alterations were seen also in unaffected Lkb1 ϩ/Ϫ mucosa, however, the Peutz-Jeghers and incipient polyp epithelium was much less differentiated and more proliferative.…”

Section: Discussioncontrasting

confidence: 42%

Impaired Gastric Gland Differentiation in Peutz-Jeghers Syndrome

Udd

Katajisto

Kyyrönen

et al. 2010

The American Journal of Pathology

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Gastrointestinal hamartomatous polyps in the PeutzJeghers cancer predisposition syndrome and its mouse model (Lkb1؉/؊ ) are presumed to contain all cell types native to the site of their occurrence. This study aimed to explore the pathogenesis of PeutzJeghers syndrome polyposis by characterizing cell types and differentiation of the epithelium of gastric polyps and predisposed mucosa. Both antral and fundic polyps were characterized by a deficit of pepsinogen C-expressing differentiated gland cells (antral gland, mucopeptic, and chief cells); in large fundic polyps, parietal cells were also absent. Gland cell loss was associated with an increase in precursor neck cells, an expansion of the proliferative zone, and an increase in smooth muscle ␣-actin expressing myofibroblasts in the polyp stroma. Lack of pepsinogen C-positive gland cells identified incipient polyps, and even the unaffected mucosa of young predisposed mice displayed an increase in pepsinogen C negative glands (25%; P ‫؍‬ 0045). In addition, in small intestinal polyps, gland cell differentiation was defective, with the absence of Paneth cells. There were no signs of metaplastic differentiation in any of the tissues studied, and both the gastric and small intestinal defects were seen in Lkb1 ؉/؊ mice, as well as polyps from patients with Peutz-Jeghers syndrome. These results identify impaired epithelial differentiation as the earliest pathological sign likely to contribute to tumorigenesis in individuals with inherited Lkb1 mutations. (Am J

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Section: Discussioncontrasting

confidence: 42%

Impaired Gastric Gland Differentiation in Peutz-Jeghers Syndrome

Udd

Katajisto

Kyyrönen

et al. 2010

The American Journal of Pathology

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“…The unattached daughter cell could die as a result of extrusion and loss of anchorage, but the loss of appropriate apoptotic mechanisms typical of cancer cells might prevent this (Slattum et al, 2009). Alternatively, it could adhere to the cell below it, resulting in vertical tissue expansion and tissue hyperplasia, which is considered a premalignant change (Fitzgibbons et al, 1998;Jones and Young, 1994;Tobi, 1999). Finally, if the tissue geometry favored the creation of a lumen, it might result in the formation of a new gland.…”

Section: Disorganization Of Tissue Morphology and Promotion Of Metastmentioning

confidence: 99%

Mitotic spindle misorientation in cancer – out of alignment and into the fire

Pease

Tirnauer

2011

Journal of Cell Science

130

103

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Patterns of spindle orientationIn most epithelia, the common pattern of spindle orientation is planar, in which the spindle is aligned along the tissue plane, SummaryMitotic spindle orientation can influence tissue organization and vice versa. Cells orient their spindles by rotating them parallel or perpendicular to the cell -and hence the tissue -axis. Spindle orientation in turn controls the placement of daughter cells within a tissue, influencing tissue morphology. Recent findings implicating tumor suppressor proteins in spindle orientation bring to the forefront a connection between spindle misorientation and cancer. In this Commentary, we focus on the role of three major human tumor suppressors -adenomatous polyposis coli (APC), E-cadherin and von Hippel-Lindau (VHL) -in spindle orientation. We discuss how, in addition to their better-known functions, these proteins affect microtubule stability and cell polarity, and how their loss of function causes spindles to become misoriented. We also consider how other cancer-associated features, such as oncogene mutations, centrosome amplification and the tumor microenvironment, might influence spindle orientation. Finally, we speculate on the role of spindle misorientation in cancer development and progression. We conclude that spindle misorientation alone is unlikely to be tumorigenic, but it has the potential to synergize with cancer-associated changes to facilitate genomic instability, tissue disorganization, metastasis and expansion of cancer stem cell compartments. Journal of Cell Scienceparallel to the apical and basal surfaces of the cell (Fernández-Miñán et al., 2007; Fischer et al., 2006; Fleming et al., 2007;Lu et al., 2001) (Fig. 1). Planar spindle orientation leads to the establishment of a cytokinetic furrow that bisects the apical and basal cell surfaces, thereby generating daughter cells that are side by side in the tissue. Both daughter cells retain or re-establish contact with the extracellular matrix (ECM), and they attach to each other along their lateral surfaces (Jinguji and Ishikawa, 1992). Because daughter cells inherit identical contents and ECM attachments, planar spindle orientation can result in symmetric cell division ( Fig. 2A). Loss of planar orientation in tumors could disrupt epithelial tissue morphology by placing daughter cells one on top of the other, creating vertical tissue expansion.Although planar spindle orientation can result in symmetric cell division, it can also lead to asymmetric cell division. For example, in the developing mammalian brain, dividing cells can show planar spindle orientation, but partition cellular components -such as the apical surface and the basal process connecting it to the ECM, unequally -resulting in asymmetric cell division (Kosodo et al., 2004; Kosodo et al., 2008;Siller and Doe, 2009). Uneven distribution of microenvironmental factors, such as gradients of growth factors, could also influence the fates of daughter cells. This might be the case in intestinal crypts, where we found planar spindl...

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“…The category "benign polyp" includes hyperplastic, inflammatory, and other non-neoplastic polyps and accounts for one-third of the total number of polyps. 23 In the model, polyps arise in the colon and the rectum stochastically through a non-homogenous Poisson process. 24 The incidence of polyps increases with age and is a function of several risk factors including gender, BMI, and family history.…”

mentioning

confidence: 99%