Stromal Myofibroblasts Predict Disease Recurrence for Colorectal Cancer

Tsujino, Toshiaki; Seshimo, Iwao; Yamamoto, Hirofumi; Ngan, Chew Yee; Ezumi, Kiyoshi; Takemasa, Ichiro; Ikeda, Masataka; Sekimoto, Mitsugu; Matsuura, Nariaki; Monden, Morito

doi:10.1158/1078-0432.ccr-06-2191

Cited by 310 publications

(252 citation statements)

References 26 publications

(21 reference statements)

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“…64 SPARC (secreted protein, acidic and rich in cysteine) expression by peritumoral fibroblasts portends a poorer prognosis for patients with resectable pancreatic cancer 65 and a-SMA expression by myofibroblasts predict disease recurrence in colorectal cancer. 66 The proinvasive activity of human myofibroblasts in vitro was shown by De Wever et al 16 using human colon cancer cells and myofibroblasts isolated from surgical colon cancer fragments. In 48-hr cultures, the colon cancer cells invaded the collagen gels only when myofibroblasts were added.…”

Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 94%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

625

601

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Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.

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Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 94%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

625

601

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“…Proteomic screening confirmed the overexpression of several proteins that have previously been shown by other methods to be highly expressed in tumor or tumoral stroma. An example of one of these proteins was α-smooth muscle actin, a marker of stromal cell activation that has been linked to poor prognosis in colon cancer [8] and is present in stromal myofibroblasts in several tumor types [3]. The proteomic screen also showed over-expression of novel proteins such as the 14-3-3 proteins which are phospho-serine/phosphothreonine-binding proteins that may promote cell survival and have been suggested to be a possible target for therapies aimed at enhancing killing of cancer cells [20].…”

Section: Proteins Under-expressed In the Tumoral Liver Tissue Comparementioning

confidence: 99%

“…14-3-3 protein has recently been shown to have a role as an adaptor protein involved in p53 stabilization and thus in regulation of apoptosis [7]. α-SMA is over-expressed in fibrotic tissue and many tumors and has a strong correlation with prognosis in colon cancer for example [8]. Periostin has been detected in several tumor types and has recently been reported to be highly expressed in fibroblasts derived from cholangiocarcinomas and also to correlate with prognosis [9].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

Darby

Vuillier-Devillers

Pinault

et al. 2010

Cancer Microenvironment

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Cholangiocarcinoma is an adenocarcinoma of the liver which has increased in incidence over the last thirty years to reach similar levels to other liver cancers. Diagnosis of this disease is usually late and prognosis is poor, therefore it is of great importance to identify novel candidate markers and potential early indicators of this disease as well as molecules that may be potential therapeutic targets. We have used a proteomic approach to identify differentially expressed proteins in peripheral cholangiocarcinoma cases and compared expression with paired non-tumoral liver tissue from the same patients. Two-dimensional fluorescence difference gel electrophoresis after labeling of the proteins with cyanines 3 and 5 was used to identify differentially expressed proteins. Overall, of the approximately 2,400 protein spots visualised in each gel, 172 protein spots showed significant differences in expression level between tumoral and non-tumoral tissue with p<0.01. Of these, 100 spots corresponding to 138 different proteins were identified by mass spectrometry: 70 proteins were over-expressed whereas 68 proteins were under-expressed in tumoral samples compared to nontumoral samples. Among the over-expressed proteins, immunohistochemistry studies confirmed an increased expression of 14-3-3 protein in tumoral cells while α-smooth muscle actin and periostin were shown to be overexpressed in the stromal myofibroblasts surrounding tumoral cells. α-Smooth muscle actin is a marker of myofibroblast differentiation and has been found to be a Ian A. Darby, Karine Vuillier-Devillers, and Émilie Pinault have equally contributed to this work.

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“…Stromal desmoplasia may enhance the invasive and metastatic potential of tumors (Tsujino et al, 2007), whereas peritumoral inflammatory reaction may be associated with a favorable prognosis in cancer patients, including those with cervical cancer (Kainz et al, 1994;Fregnani et al, 2007;Jass et al, 2007). In our previous study, stromal desmoplasia and peritumoral inflammatory reaction were not predictive of the prognosis in early-stage cervical cancer patients (Khunamornpong et al, 2013).…”

Section: Introductionmentioning

confidence: 80%

“…While the spraylike invasive pattern is reflective of an intrinsic property of cancer cells for dissociation and dissemination (Horn et al, 2006a), inflammatory reaction could represent a host response against tumor cells (Kainz et al, 1994;Fregnani et al, 2007) and may have a role in limiting direct extension of tumor or LVSI (Khunamornpong et al, 2013). As an inflammatory reaction seems to prevent stromal desmoplasia (Khunamornpong et al, 2013), it might help reduce one of the factors that promote tumor growth and spread (Tsujino et al, 2007). It is possible that the interaction of these features of invasive margin would contribute to the prognosis in individual patients.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Model in Patients with Early-stage Squamous Cell Carcinoma of the Uterine Cervix: A Combination of Invasive Margin Pathological Characteristics and Lymphovascular Space Invasion

Khunamornpong

Lekawanvijit²,

Settakorn³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: This study aimed to develop a prognostic model in patients with early-stage cervical squamous cell carcinoma based on clinicopathological features, including invasive margin characteristics. Materials and Methods: Clinicopathological features and outcomes of 190 patients with FIGO stage IB-IIA cervical squamous cell carcinoma treated by surgery were collected and analyzed for factors associated with tumor recurrence. In addition to well-recognized pathological risk factors, the pathological characteristics of invasive margin (type of invasive pattern and degree of stromal desmoplasia and peritumoral inflammatory reaction) were also included in the analysis. Multiple scoring models were made by matching different clinicopathological variables and/ or different weighting of the score for each variable. The model with the best performance in the prediction of recurrence and decreased survival was selected. Results: The model with the best performance was composed of a combined score of invasive pattern, lymphovascular space invasion (LVSI), and degree of inflammatory reaction and stromal desmoplasia (total score =10). Compared to those with score ≤8, the patients with score 9-10 had a significantly higher recurrence rate in the overall group (p<0.001) and the subgroup without adjuvant therapy (p<0.001), while the significance was marginal in the subgroup with adjuvant therapy (p=0.069). In addition, the patients with score 9-10 had a higher rate of tumor recurrence at distant sites (p=0.007). The disease-free survival was significantly lower in the patients with score 9-10 than those with score ≤8 among the overall patients (p<0.001), in the subgroup without adjuvant therapy (p<0.001), and the subgroup with adjuvant therapy (p=0.047). Conclusions: In this study, a prognostic model based on a combination of pathological characteristics of invasive margin and LVSI proved to be predictive of tumor recurrence and decreased disease-free survival in patients with early-stage cervical squamous cell carcinoma.

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Stromal Myofibroblasts Predict Disease Recurrence for Colorectal Cancer

Cited by 310 publications

References 26 publications

Stromal myofibroblasts are drivers of invasive cancer growth

Stromal myofibroblasts are drivers of invasive cancer growth

Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

Prognostic Model in Patients with Early-stage Squamous Cell Carcinoma of the Uterine Cervix: A Combination of Invasive Margin Pathological Characteristics and Lymphovascular Space Invasion

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