Clinicopathological significance of fibrotic capsule formation around liver metastasis from colorectal cancer

Lunevičius, Raimundas; Nakanishi, Hayao; Ito, Seiji; Kozaki, Ken Ichi; Kato, Tomoyuki; Tatematsu, Masae; Yasui, Kenzo

doi:10.1007/s004320000199

Cited by 91 publications

(80 citation statements)

References 20 publications

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“…Such a deposition of fibrotic material has been reported in activated cultured myofibroblasts 25 as well as for human metastases of colorectal origin, where the formation of fibrotic capsules surrounding the tumor has been found in 20% within a group of 69 examined cases. 26 On the one hand, such ECM deposition may have an antitumor defensive function as indicated by the better prognosis if capsules have formed around colorectal liver metastases 26 or the fact that less liver metastases are formed in cirrhotic livers. 27 On the other hand, ECM deposition seems to provide proinvasive signals.…”

Section: Discussionmentioning

confidence: 99%

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Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases

Bandapalli

Geheeb

Kobelt

et al. 2005

Intl Journal of Cancer

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Host cell reactions are a crucial determinant for tumor invasion. We analyzed on a genomewide scale gene expression differences between microdissected tissues taken from unaffected liver tissue of a human colorectal tumor (LS174) growing in the livers of nude mice and tissue from the host part of the invasive front. Due to the low degree of interspecies cross‐hybridization of 15% as determined on Affymetrix microarrays, our xenograft model allowed for the distinction of genes of murine versus human origin even if the respective tissues could not be isolated separately. Using the gene ontology (GO) classification, we were able to determine patterns of up‐ and downregulated genes in the liver part of the invasive front. We observed a pronounced overrepresentation, e.g., of the GO terms “extracellular matrix,” “cell communication,” “response to biotic stimulus,” “structural molecule activity” and “cell growth,” indicating a very pronounced host cell response to tumor invasion. On the single gene level, hepatic stellate cell (HSC) activation markers were overrepresented in the liver part of the invasion front. Immunohistochemistry and qPCR confirmed an activation of HSC as well as an increased number of HSC in the invasive front as compared to the noninvaded liver tissue. In summary, our data demonstrate the feasibility of an interspecies differential gene expression approach on a genomewide scale. © 2005 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

“…Similar results of HSC-specific immunoreactivity have been found for human specimen. 26,44 The tropomyosins stabilize actin fibers and the a-actinins are actin crosslinking proteins, which are responsible for the formation of contractile bundles. They are concentrated in stress fibers, which they hold in contact to the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases

Bandapalli

Geheeb

Kobelt

et al. 2005

Intl Journal of Cancer

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“…The invasive margin of the primary cancers were classified as either pushing or infiltrative based on the predominant morphology, as defined by Jass et al (1987). A modified classification based on Yasui ( Lunevicius et al, 2001) was used for liver metastases, with metastases being classified as capsulated if 450% of the margin exhibited a fibrous capsule separating tumour from stroma.…”

Section: Histochemical Analysis Of the Invasive Marginmentioning

confidence: 99%

The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases

et al. 2007

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The nature of the invasive growth pattern and microvessel density (MVD) have been suggested to be predictors of prognosis in primary colorectal cancer (CRC) and colorectal liver metastases. The purpose of the present study was to determine whether these two histological features were interrelated and to assess their relative influence on disease recurrence and survival following surgical resection. Archival tissue was retrieved from 55 patients who had undergone surgical resection for primary CRC and matching liver metastases. The nature of the invasive margin was determined by haematoxylin and eosin (H&E) histochemistry. Microvessel density was visualised using immunohistochemical detection of CD31 antigen and quantified using image capture computer software. Clinical details and outcome data were retrieved by case note review and collated with invasive margin and MVD data in a statistical database. Primary CRCs with a pushing margin tended to form capsulated liver metastases (Po0.001) and had a significantly better disease-free survival than the infiltrative margin tumours (log rank P ¼ 0.01). Primary cancers with a high MVD tended to form high MVD liver metastases (P ¼ 0.007). Microvessel density was a significant predictor of disease recurrence in primary CRCs (P ¼ 0.006), but not liver metastases. These results suggest that primary CRCs and their liver metastases show common histological features. This may reflect common mechanisms underlying the tumour -host interaction.

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“…In liver metastasis, the local host stroma, a complex mixture of fibroblasts, myofibroblasts, endothelial cells, and inflammatory cells, is considered to play a crucial role in the infiltration and colonization of the organ by metastatic cells, such that the outcome of metastasis depends on multiple interactions of metastatic cells with the stromal cells in the liver microenvironment (4). Morphologic evidence suggest that hepatic stellate cells (HSC) contribute to the genesis of myofibroblasts surrounding colorectal liver metastases (5,6). HSCs are multifunctional liver mesenchymal cells residing around the endothelial cells in the space of Disse.…”

Section: Introductionmentioning

confidence: 99%

A Secreted Form of ADAM9 Promotes Carcinoma Invasion through Tumor-Stromal Interactions

et al. 2005

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Tumor cell invasion is a process regulated by integrins, matrix-degrading enzymes, and interactions with host tissue stromal cells. The ADAM family of proteins plays an important role in modulating various cellular responses. Here, we show that an alternatively spliced variant of ADAM9 is secreted by hepatic stellate cells and promotes carcinoma invasion. ADAM9-S induced a highly invasive phenotype in several human tumor cell lines in Matrigel assays, and the protease activity of ADAM9-S was required for invasion. ADAM9-S binds directly to A 6 B 4 and A 2 B 1 integrins on the surface of colon carcinoma cells through the disintegrin domain. ADAM9-S was also able to cleave laminin and promote invasion. Analysis of human liver metastases revealed that ADAM9 is expressed by stromal liver myofibroblasts, particularly those that are localized within the tumor stroma at the invasive front. These results emphasize the importance of tumor-stromal interactions in invasion and suggest that ADAM9-S can be an important determinant in the ability of cancer cells to invade and colonize the liver. (Cancer Res 2005; 65(11): 4728-38)

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Clinicopathological significance of fibrotic capsule formation around liver metastasis from colorectal cancer

Cited by 91 publications

References 20 publications

Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases

Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases

The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases

A Secreted Form of ADAM9 Promotes Carcinoma Invasion through Tumor-Stromal Interactions

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