Plasminogen activators and inhibitor type 1 in neoplastic colonic tissue from patients with familial adenomatous polyposis

Sier, Cornelis F.M.; Vloedgraven, H. J. M.; Griffioen, G.; Ganesh, S.; Nagengast, F. M.; Lamers, C. B. H. W.; Verspaget, H. W.

doi:10.1038/bjc.1995.80

Cited by 20 publications

(11 citation statements)

References 21 publications

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“…Increased levels of uPA in tumour tissue from patients have been associated with an overall poor prognosis 8–10. Additional studies in patients with familial adenomatous polyposis (FAP), an inherited form of colon cancer, indicated that uPA levels are higher during the transition from normal‐appearing colonic mucosa to neoplastic lesions, thus implicating uPA in the early stages of tumour development 11.…”

Section: Introductionmentioning

confidence: 99%

A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc^Min/+ mice

Ploplis¹,

Tipton²,

Menchen³

et al. 2007

The Journal of Pathology

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The interaction of urokinase-type plasminogen activator (uPA) and its receptor, uPAR, on cell surfaces facilitates the generation of cell-bound plasmin, thus allowing cells to establish a proteolytic front that enables their migration through protein barriers. This complex also activates cell signalling pathways that influence cell functions. Clinical studies have identified uPA as an indicator of poor overall survival in patients with colorectal cancer. In the current study, a mouse model of colon cancer, Apc(Min/+), with an additional deficiency of uPA (Apc(Min/+)/Plau-/-) was used to determine the effects of uPA on tumour initiation and growth. Utilizing this model, it was found that the number of tumours was diminished in these mice relative to Apc(Min/+) mice, which correlated with the decreased leukocyte infiltration in the tumours. However, tumour growth was not impeded in Apc(Min/+)/Plau-/- mice, and proliferation and tumour vascularization were, in fact, enhanced in Apc(Min/+)/Plau-/- mice. These latter effects are consistent with a mechanism involving up-regulation of COX-2 expression and Akt pathway activation in Apc(Min/+)/Plau-/- mice. The results from this study suggest that uPA plays dual and opposing roles in regulating lesion development: one early, during the transition from normal epithelia to dysplastic lesions, and another later during tumour growth.

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Section: Introductionmentioning

confidence: 99%

A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc^Min/+ mice

Ploplis¹,

Tipton²,

Menchen³

et al. 2007

The Journal of Pathology

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“…Sonoshita et al [96] studied murine and human tissue and showed that the transcriptional modulator enhancer of split (Aes) prevented CRC cells from intravasation through the impairment of trans-endothelial invasion that followed Notch-dependent mechanisms. Concurrently, urokinase plasminogen activator (uPA) expression is increased in patients with FAP during the transformation of normal to dysplastic epithelia [97,98] . The uPA system consists of uPA, the uPA receptor (uPAR), the tissue-type plasminogen activator (tPA), the plasminogen (Plg) and plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2).…”

Section: Survival In the Lymphatic And/or The Blood Vesselsmentioning

confidence: 99%

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Paschos

Majeed

Bird

2014

WJG

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Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting. Paschos KA, Majeed AW, Bird NC. Natural history of hepatic metastases from colorectal cancer -pathobiological pathways with clinical significance.

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“…5,19,21,38 The ability of cells to survive in the face of loss of cell contact is a marker of tumor progression, 13 and malignant transformation, invasion, and metastasis are linked to future somatic mutations, activation of oncogenes, inactivation of tumor suppresser genes, and upregulation of plasminogen activators and inhibitors. 33,35 Adenomas and carcinomas are derived from undifferentiated crypt stem cells, which retain their ability for multidirectional differentiation. Ninety-two percent of FAP carcinomas have Paneth cell differentiation, 99% have endocrine differentiation, and the number of well-differentiated mucus-secreting cells in dysplastic epithelium has been considered an indicator of the severity of the lesion.…”

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confidence: 99%

Characterization of Metastatic Intestinal Adenocarcinoma with Differentiation into Multiple Morphologic Cell Types in a Virginia Opossum

Prater¹,

Duncan²,

Gaydos³

1999

Vet Pathol

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Abstract.A captively maintained mature male opossum (Didelphis virginiana) utilized in a research protocol was presented with clinical signs of chronic diarrhea and severe muscle wasting. At necropsy, there was multifocal mural gastric, intestinal, and urinary bladder thickening, concurrent bilateral hydroureter and hydronephrosis, and extensive fibrous abdominal adhesions. Histologic evaluation revealed intestinal adenocarcinoma with coelomic metastasis to the stomach and urinary bladder. The adenocarcinoma was evaluated using histochemistry and electron microscopy. Paneth, enteroendocrine, and goblet cell differentiation was documented in primary and metastatic sites. This unique presentation of intestinal adenocarcinoma has not previously been reported in the opossum or any other animals. Intestinal neoplasia with Paneth cell differentiation is extremely rare and has been reported in humans with familial adenomatous polyposis.Key words: Adenocarcinoma; enteroendocrine cell; goblet cell; histochemistry; immunohistochemistry; intestine; neoplasia; opossums; Paneth cell; transmission electron microscopy.Recently, various species of opossums have become important laboratory animal models of human disease in immunology and endocrinology research. 8,32 Because maintenance of captive-bred colonies is difficult, most opossums of the genus Didelphis used in research are captured from the wild and are entered into research projects with unknown age and medical history. 32 Consequently, unquantifiable variability is inherent in disease modeling systems in opossums. Demographic information on opossum infectious and neoplastic diseases is sparse, and more knowledge of common or unique marsupial diseases is imperative for proper evaluation of marsupials utilized in medical research. Here, we describe a case of metastatic intestinal adenocarcinoma with differentiation into multiple cell types in a Virginia opossum (Didelphis virginiana) and compare these observations with those reported for domestic animals and humans.A captive, mature, approximately 2-year-old male Virginia opossum presented with poor body condition and a history of chronic diarrhea and loss of muscle mass. No obvious abnormalities were detected on the clinical biochemical profile. Congestive heart failure was suspected because it had been documented in five other opossums from the same captive colony. Euthanasia was performed following poor response to supportive care and marked debility.Postmortem examination revealed multiple areas of mural thickening throughout the stomach, small and large intestine, ureters, and urinary bladder. There was also bilateral hydronephrosis with multifocal subcapsular hemorrhage, diffuse enlargement of the liver, marked pulmonary atelectasis, and numerous fibrous peritoneal adhesions. No gross cardiac abnormalities were observed.Histologic evaluation of duodenum revealed transmural infiltration of a pleomorphic population of cuboidal to columnar epithelial cells arranged in small nests with occasional glandular profiles, an...

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Plasminogen activators and inhibitor type 1 in neoplastic colonic tissue from patients with familial adenomatous polyposis

Cited by 20 publications

References 21 publications

A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc^Min/+ mice

A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc^Min/+ mice

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Characterization of Metastatic Intestinal Adenocarcinoma with Differentiation into Multiple Morphologic Cell Types in a Virginia Opossum

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Plasminogen activators and inhibitor type 1 in neoplastic colonic tissue from patients with familial adenomatous polyposis

Cited by 20 publications

References 21 publications

A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in ApcMin/+ mice

A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in ApcMin/+ mice

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Characterization of Metastatic Intestinal Adenocarcinoma with Differentiation into Multiple Morphologic Cell Types in a Virginia Opossum

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A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc^Min/+ mice

A urokinase‐type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc^Min/+ mice