Clinical Implications of Fibroblast Activation Protein in Patients with Colon Cancer

@article{Henry2007ClinicalIO,
  title={Clinical Implications of Fibroblast Activation Protein in Patients with Colon Cancer},
  author={Leonard R. Henry and Hyung Ok Lee and John S. Lee and Andres J Klein-Szanto and Perry Watts and Eric A. Ross and Wen‐Tien Chen and Jonathan D. Cheng},
  journal={Clinical Cancer Research},
  year={2007},
  volume={13},
  pages={1736 - 1741}
}
Purpose: Human fibroblast activation protein (FAP)/seprase is a 97-kDa surface glycoprotein expressed on tumor associated fibroblasts in the majority of epithelial cancers including colon adenocarcinomas. FAP overexpression in human tumor cells has been shown to promote tumor growth in animal models, and clinical trials targeting FAP enzymatic activity have been initiated. The primary objective of this study was to evaluate the clinical significance of stromal FAP in human colon cancers by… 

Figures and Tables from this paper

Clinical Findings on Fibroblast Activation Protein in Patients with Gastric Cancer
TLDR
Human fibroblast activation protein (FAP), a 97-kDa surface glycoprotein expressed in tumor-associated fibroblasts, is examined in surgically resected gastric carcinomas and their association with clinicopathological findings and prognosis indicates that vessel invasion is connected with the expression of F AP and that a positive finding of FAP confer a worse prognosis in the patients with gastric cancer.
High expression of fibroblast activation protein is an adverse prognosticator in gastric cancer
TLDR
Patients whose gastric tumors have high level of FAP expression were more likely to have aggressive disease development and poor survival and studies that elucidate the mechanism of how the FAP positive cells promote gastric cancer development are needed.
Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance.
TLDR
FAP is highly expressed in carcinoma cells and fibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.
Fibroblast activation protein and its prognostic significance in correlation with vascular endothelial growth factor in pancreatic adenocarcinoma.
TLDR
Multivariate analysis demonstrated the prognostic superiority of FAP over VEGF, which is considered to be the most consistently reproducible molecular marker with prognostic value in resected pancreatic adenocarcinoma.
Clinical implications of fibroblast activation protein-α in non-small cell lung cancer after curative resection: a new predictor for prognosis
TLDR
Elevated FAP-α expression may be associated with inflammation and suppressed lymphocyte-dependent immune response, which then result in the tumor progression, and its high expression is a predictor of poor survival of NSCLC patients.
Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice.
TLDR
Results indicate that FAP depletion inhibits tumor cell proliferation indirectly, increases accumulation of collagen, decreases myofibroblast content, and decreases blood vessel density in tumors, providing proof of principle that targeting stromal cell-mediated modifications of the tumor microenvironment may be an effective approach to treating epithelial-derived solid tumors.
Fibroblast Activation Protein and Its Relationship to Clinical Outcome in Pancreatic Adenocarcinoma
TLDR
Fibroblast activation protein is highly expressed in pancreatic adenocarcinoma, with greatest expression immediately adjacent to tumor, and higher FAP expression is associated with worse clinical outcome.
Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer
TLDR
It is shown that FAP expression in EOC is associated with poorer clinical outcomes suggesting that targeting FAP could have pleiotropic anti-tumor effects, and anti-FAP therapy could be a highly effective novel treatment for EOC, especially in cisplatinum-resistant cases.
High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis
TLDR
Stromal F AP expression is common in colorectal cancer, and it is concluded that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.
Fibroblast activation protein-α promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions
TLDR
In vitro studies revealed that cells expressing wild type FAP or FAPS624A degrade extracellular matrix more extensively, accumulate higher levels of matrix metalloproteinase-9 (MMP-9) in conditioned medium, are more invasive in type I collagen gels, and have altered signaling compared to control transfectants that do not express FAP and form slow growing tumors.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 41 REFERENCES
Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers.
TLDR
The results suggest that the F19+ phenotype correlates with specialized fibroblast functions in wound healing and malignant tumor growth, and may serve as a target for antibodies labeled with radioisotopes or toxic agents, or inflammatogenic antibodies, in carcinoma patients.
Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast
TLDR
Clinopathologic analysis revealed that more abundant FAP/seprase expression in 112 cases of invasive ductal carcinoma is associated with longer overall and disease‐free survival, and multivariate analysis with other clinicopathologic factors demonstrated that F AP/sePRase expression is an independent prognostic factor.
Promotion of tumor growth by murine fibroblast activation protein, a serine protease, in an animal model.
TLDR
The ability of F AP to potentiate tumor growth in an animal model is demonstrated and a possible therapeutic role for functional inhibition of FAP activity is suggested.
Fibroblast Activation Protein, a Dual Specificity Serine Protease Expressed in Reactive Human Tumor Stromal Fibroblasts*
TLDR
It is demonstrated that FAP is present as an active cell surface-bound collagenase in epithelial tumor stroma and opens up investigation into physiological substrates of its novel, tumor-associated dipeptidyl peptidase activity.
Seprase promotes rapid tumor growth and increased microvessel density in a mouse model of human breast cancer.
TLDR
Seprase-expressing cells are better able to attract blood vessels and exhibit rapid tumor growth, and microvessel density is elevated in tumors of two different lines of seprase transfectants.
The Expression of a Type II Transmembrane Serine Protease (Seprase) in Human Gastric Carcinoma
TLDR
The studies showed the unique expression and localization of seprase in the tumor and stromal cells within human gastric carcinoma but not in normal tissues, suggesting a role of sepsis in the invasive and metastatic progression of gastric cancer.
Morphoproteomic and pharmacoproteomic correlates in hormone-receptor-negative breast carcinoma cell lines.
TLDR
A close association between the immunohistochemical expression of signal transduction markers and in vitro inhibition by pharmaceutical agents is shown, and correlations between the sites of action of the pharmaceutical agents and the downstream expression of proteins in hormone-receptor-negative breast cancer cell lines are correlations.
Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth
TLDR
The results indicate that the enzymatic activity of fibroblast activation protein is necessary for fibro Blast activation protein–driven tumor growth in the HEK293 xenograft model system, and establishes the proof-of-principle that this protein plays an important role in the promotion of tumor growth.
Stromal Antigen Targeting by a Humanised Monoclonal Antibody: An Early Phase II Trial of Sibrotuzumab in Patients with Metastatic Colorectal Cancer
TLDR
Unconjugated sibrotuzumab (BIBH 1), which is a humanised version of the murine anti-FAP mAb F19, was investigated for its anti-tumour activity, safety and pharmacokinetics and was well tolerated and safe.
Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infection.
TLDR
FAP expression identifies a HSC subpopulation at the tissue-remodelling interface that is related to the severity of liver fibrosis, as well as a correlation between FAP expression and necroinflammatory score.
...
1
2
3
4
5
...