Metastasis‐related factors expressed in pT1 pN0 breast cancer: Assessment of recurrence risk

Ogura, Shigeto; Ohdaira, Takeshi; Hozumi, Yasuo; Omoto, Yoko; Nagai, Hideo

doi:10.1002/jso.20805

Cited by 18 publications

(8 citation statements)

References 54 publications

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“…The expression of MMP-14 correlates with the malignancy of different tumor types (29,30), and its overexpression in tumor cell lines enhances their invasiveness in vitro and tumorigenicity in vivo (5,31). Therefore, MMP-14 is an important target for the development of a highly selective MMP inhibitor for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…MMP-14 drives invasion by functioning as a pericellular collagenase (2) and an activator of proMMP-2 (3,4), and is directly linked to tumorigenesis and metastasis (5)(6)(7). MMP-14 null mice display impaired basic fibroblast growth factor-mediated corneal angiogenesis (4), and tissues from the same mice fail to show angiogenesis in a type I collagen ex vivo model, supporting a potential role of MMP-14 in angiogenesis as well (8).…”

Section: Introductionmentioning

confidence: 99%

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Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

et al. 2009

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“…In the present study, by applying diagnostic ROC curve for VEGF data, the area under curve was 0.502, which statically considered as diagonal marker that cannot discriminate patients with breast cancer than controls. However, Ogura et al [30] stated that VEGF could be considered as a predictor risk factor of recurrence in the early stage of breast cancer.…”

Section: Resultsmentioning

confidence: 98%

Significance of vascular endothelial growth factor, interleukin-18 and nitric oxide in patients with breast cancer: correlation with carbohydrate antigen 15.3

2010

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The aim of this study was to determine serum concentrations of angiogenic factors including vascular endothelial growth factor (VEGF), interleukin 18 (IL-18) and nitric oxide (NO) in patients with breast cancer and to evaluate whether these factors will be correlated with CA 15.3, as a routine tumor marker for breast cancer or not. This study was conducted on 44 patients with breast cancer and 15 healthy individuals as a control group. The results demonstrated significant increase in serum IL-18, NO and CA 15.3 levels in sera of breast cancer patients when compared to those of the control group (P < 0.001, P = 0.016 and P < 0.001, respectively). However, the mean serum level of VEGF in patients as showed insignificant increase compared to that of the controls was not significant (P = 0.311). Sensitivity of CA 15.3, VEGF, IL-18 and NO to detect patients with disease was 52.2, 21.3, 77.2 and 70.4 %, respectively. In addition, positive status of serum CA 15.3 and/or IL-18 was found in 39 out of 44 (88.6 %) patients, and the positive status of serum CA 15.3 and/or NO was only found in 35 out of 44 (79.5 %). In conclusion, the simultaneous determination of IL-18 or NO in combination with the CA 15.3 may increase the sensitivity to diagnose breast cancer and may aid in disease prognosis.

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“…MT1-MMP is thought to be a promising predictor for recurrence risk in early stage breast cancer. (25) Although accumulation of 111 In-MT1-scFv and 111 In-MT1-diabody in abdominal tissues like kidney, liver, spleen and intestine for excretion would hamper imaging tumors, we expect both probes to be used for breast cancer imaging, which is less affected by the background radioactivity of surrounding tissues because breast cancers are typically located from these other tissues.…”

Section: Discussionmentioning

confidence: 99%

Miniaturized antibodies for imaging membrane type‐1 matrix metalloproteinase in cancers

et al. 2013

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Since membrane type-1 matrix metalloproteinase (MT1-MMP) plays pivotal roles in tumor progression and metastasis and holds great promise as an early biomarker for malignant tumors, a method of evaluating MT1-MMP expression levels would be valuable for molecular biological and clinical studies. Although we have previously developed a 99m Tc-labeled anti-MT1-MMP monoclonal IgG ( 99m Tc-MT1-mAb) as an MT1-MMP imaging probe by nuclear medical techniques for this purpose, slow pharmacokinetics were a problem due to its large molecular size. Thus, in this study, our aim was to develop miniaturized antibodies, a single chain antibody fragment (MT1-scFv) and a dimer of two molecules of scFv (MT1-diabody), as the basic structures of MT1-MMP imaging probes followed by in vitro and in vivo evaluation with an 111 In radiolabel. Phage display screening successfully provided MT1-scFv and MT1-diabody, which had sufficiently high affinity for MT1-MMP (K D = 29.8 and 17.1 nM). Both 111 In labeled miniaturized antibodies showed higher uptake in MT1-MMP expressing HT1080 cells than in non-expressing MCF7 cells. An in vivo biodistribution study showed rapid pharmacokinetics for both probes, which exhibited >20-fold higher tumor to blood radioactivity ratios (T ⁄ B ratio), an index for in vivo imaging, than 99m Tc-MT1-mAb 6 h post-administration, and significantly higher tumor accumulation in HT1080 than MCF7 cells. SPECT images showed heterogeneous distribution and ex vivo autoradiographic analysis revealed that the radioactivity distribution profiles in tumors corresponded to MT1-MMP-positive areas. These findings suggest that the newly developed miniaturized antibodies are promising probes for detection of MT1-MMP in cancer cells. (Cancer Sci 2013; 104: 495-501) T umor metastasis is the most frequent cause of death for cancer patients. In order to metastasize, tumor cells must acquire the ability to break through the basement membrane and invade dense networks of interstitial ECM proteins.(1) Matrix metalloproteinases (MMPs) are a family of enzymes responsible for degrading the various ECM components. While most MMPs are secreted as soluble zymogens, members of the subfamily of membrane-type MMPs (MT-MMPs) anchored to the cell membrane are suited for pericellular proteolysis. MT1-MMP is the major pericellular protease involved in processing triple helical collagen type I.(4) In addition, MT1-MMP activates MMP zymogens such as proMMP-2 and proMMP-13 that have significant involvement in tumor cell invasion and metastasis.(5,6) As MT1-MMP has a close relationship with tumor malignancy and holds great promise as an early biomarker of malignant tumors, (7,8) in vivo monitoring and ⁄ or quantitation of MT1-MMP expression could be valuable tools for molecular biological and clinical studies.Recently, in the course of focusing on nuclear medical techniques for noninvasive quantitative evaluation of biological molecules deep within the body, we developed a 99m Tc-labeled anti-MT1-MMP monoclonal IgG ( 99m Tc-MT1-mAb) as a radiolabeled...

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Metastasis‐related factors expressed in pT1 pN0 breast cancer: Assessment of recurrence risk

Abstract: MMP family and growth factors may be promising predictors of recurrence risk of early stage breast cancer.

Cited by 18 publications

References 54 publications

Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

Significance of vascular endothelial growth factor, interleukin-18 and nitric oxide in patients with breast cancer: correlation with carbohydrate antigen 15.3

Miniaturized antibodies for imaging membrane type‐1 matrix metalloproteinase in cancers

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