Local Increase in Polymorphonuclear Leukocyte Elastase Is Associated With Tumor Invasiveness in Non-small Cell Lung Cancer

Yamashita, Jun‐ichi; Tashiro, Kotaro; Yoneda, Satoshi; Kawahara, Katsunobu; Shirakusa, Takayuki

doi:10.1378/chest.109.5.1328

Cited by 39 publications

(22 citation statements)

References 20 publications

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“…Recently, PMN elastase was shown to be present in human colorectal carcinoma with particular enrichment at the tumor-host interface (42). Also, breast and non-small cell lung cancer cells are known to secrete PMN elastase in vitro (43,44). Possibly, human TrpRS secreted from apoptotic cells may be cleaved by PMN elastase at the tumor-host interface.…”

Section: Discussionmentioning

confidence: 99%

A human aminoacyl-tRNA synthetase as a regulator of angiogenesis

Wakasugi

Slike

Hood

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

248

277

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Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis. It was shown recently that human tyrosyl-tRNA synthetase (TyrRS) can be split into two fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. Tryptophanyl-tRNA synthetase (TrpRS) is a close homologue of TyrRS. A natural fragment, herein designated as mini TrpRS, was shown by others to be produced by alternative splicing. Production of this fragment is reported to be stimulated by IFN-␥, a cytokine that also stimulates production of angiostatic factors. Mini TrpRS is shown here to be angiostatic in a mammalian cell culture system, the chicken embryo, and two independent angiogenesis assays in the mouse. The full-length enzyme is inactive in the same assays. Thus, protein synthesis may be linked to the regulation of angiogenesis by a natural fragment of TrpRS.

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Section: Discussionmentioning

confidence: 99%

A human aminoacyl-tRNA synthetase as a regulator of angiogenesis

Wakasugi

Slike

Hood

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

248

277

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“…Supernatants from leukocyte elastase is associated with tumor invasiveness in many types of cancer. 22 Whereas type XVIII trimerbodies were completely degraded by both proteases, type XV trimerbodies maintained their molecular integrity. Structurally intact type XV Serum stability.…”

Section: Methodsmentioning

confidence: 98%

Improved stability of multivalent antibodies containing the human collagen XV trimerization domain

Cuesta

Sánchez-Martín

Blanco-Toribio

et al. 2012

mAbs

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“…Tumour growth and angiogenesis are associated with a strong inflammatory response via the attraction of macrophages and polymorphonuclear (PMN) leukocytes by tumour cell-secreted chemoattractants (Jackson et al, 1997;Lee et al, 1997). In contrast to their attributed role in exterminating the tumour, recruited inflammatory cells have been reported to be associated with tumour progression as well (Scholl et al, 1994;Yamashita et al, 1994Yamashita et al, , 1996Shamamian et al, 2000Shamamian et al, , 2001. The responsible protease is thought to be PMN-elastase (PMN-E), a serine protease that can degrade various components of the extracellular matrix directly (Janoff and Schere, 1968;Mainardi et al, 1980;McDonald and Kelley, 1980;Barrett, 1981), or indirectly through either the activation of other proteases (Machovich and Owen, 1990;Shamamian et al, 2001) or the inactivation of their inhibitors (Levin and Santell, 1987;Gramse et al, 1984;Wu et al, 1995).…”

mentioning

confidence: 99%

“…The most extensively studied protease systems involve those of the urokinase-type plasminogen activator (uPA) (reviewed by Andreasen et al, 1997;Schmitt et al, 1997a;Look and Foekens, 1999) and a variety of matrix metalloproteinases (MMPs) (reviewed by Duffy et al, 2000;Nelson et al, 2000). Similarly, high tumour levels of PMN-E have been reported to be associated with a poor prognosis in patients with primary breast cancer (Yamashita et al, 1994(Yamashita et al, , 1995a and nonsmall cell lung cancer (Yamashita et al, 1996). In addition to their prognostic relevance in primary disease, several proteases have been shown to be positive or negative predictive factors for the efficacy of adjuvant systemic endocrine therapy or chemotherapy in patients with breast cancer.…”

mentioning

confidence: 99%

Elevated expression of polymorphonuclear leukocyte elastase in breast cancer tissue is associated with tamoxifen failure in patients with advanced disease

et al. 2003

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Besides a variety of other proteases, polymorphonuclear leukocyte elastase (PMN-E) is also suggested to play a role in the processes of tumour cell invasion and metastasis. Yet, there is only limited data available on the relation between the tumour level of PMN-E and prognosis in patients with primary breast cancer, and no published information exists on its relation with the efficacy of response to systemic therapy in patients with advanced breast cancer. In the present study, we have measured with enzyme-linked immunosorbent assay the levels of total PMN-E in cytosolic extracts of 463 primary breast tumours, and have correlated their levels with the rate and duration of response on first-line tamoxifen therapy (387 patients) or chemotherapy (76 patients) in patients with locally advanced and/or distant metastatic breast cancer. Furthermore, the probabilities of progression-free survival and postrelapse survival were studied in relation to the tumour levels of PMN-E. Our results show that in logistic regression analysis for response to tamoxifen treatment in patients with advanced disease, high PMN-E tumour levels were associated with a poor rate of response compared with those with low PMN-E levels (odds ratio: OR, 0.40; 95% CI, 0.22 -0.73; P ¼ 0.003). After correction for the contribution of the traditional predictive factors in multivariate analysis, the tumour PMN-E status was an independent predictor of response (P ¼ 0.01). Furthermore, a high tumour PMN-E level was related with a poor progression-free survival (Po0.001) and postrelapse survival (P ¼ 0.002) in a time-dependent analysis. In contrast, the tumour level of PMN-E was not significantly related with the efficacy of response to first-line chemotherapy in patients with advanced breast cancer. Our present results suggest that PMN-E is an independent predictive marker for the efficacy of tamoxifen treatment in patients with advanced breast cancer.

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Local Increase in Polymorphonuclear Leukocyte Elastase Is Associated With Tumor Invasiveness in Non-small Cell Lung Cancer

Cited by 39 publications

References 20 publications

A human aminoacyl-tRNA synthetase as a regulator of angiogenesis

A human aminoacyl-tRNA synthetase as a regulator of angiogenesis

Improved stability of multivalent antibodies containing the human collagen XV trimerization domain

Elevated expression of polymorphonuclear leukocyte elastase in breast cancer tissue is associated with tamoxifen failure in patients with advanced disease

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