Matrix Metalloproteinase-9 Expression in Lung Cancer Patients and Its Relation to Serum MMP-9 Activity, Pathologic Type, and Prognosis

El-Badrawy, Mohamed K.; Yousef, Aida M.; Shaalan, Dalia; Elsamanoudy, Ayman Z.

doi:10.1097/lbr.0000000000000094

Cited by 62 publications

(46 citation statements)

References 23 publications

(17 reference statements)

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“…MMP-9 is involved in basement membrane degradation that furthers tumor invasion and metastases [42]. Past studies showed that MMP-9 s are highly elevated in LC patients, especially stage III-IV [43,44]. We also observed a correlation between IL-8 and MMP-9 levels in LC patients.…”

Section: Discussionsupporting

confidence: 61%

Blood test shows high accuracy in detecting stage I non-small cell lung cancer

Goebel¹,

Louden²,

McKenna³

et al. 2020

BMC Cancer

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Background: In a previous study (Goebel et. al, Cancer Genomics Proteomics 16:229-244, 2019), we identified 33 biomarkers for an early stage (I-II) Non-Small Cell Lung Cancer (NSCLC) test with 90% accuracy, 80.3% sensitivity, and 95.4% specificity. For the current study, we used a narrowed ensemble of 21 biomarkers while retaining similar accuracy in detecting early stage lung cancer. Methods: A multiplex platform, 486 human plasma samples, and 21 biomarkers were used to develop and validate our algorithm which detects early stage NSCLC. The training set consisted of 258 human plasma with 79 Stage I-II NSCLC samples. The 21 biomarkers with the statistical model (Lung Cancer Detector Test 1, LCDT1) was then validated using 228 novel samples which included 55 Stage I NSCLC. Results: The LCDT1 exhibited 95.6% accuracy, 89.1% sensitivity, and 97.7% specificity in detecting Stage I NSCLC on the blind set. When only NSCLC cancers were analyzed, the specificity increased to 99.1%.Conclusions: Compared to current approved clinical methods for diagnosing NSCLC, the LCDT1 greatly improves accuracy while being non-invasive; a simple, cost-effective, early diagnostic blood test should result in expanding access and increase survival rate.

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Section: Discussionsupporting

confidence: 61%

Blood test shows high accuracy in detecting stage I non-small cell lung cancer

Goebel¹,

Louden²,

McKenna³

et al. 2020

BMC Cancer

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“…Enhanced expression and upgraded activity of MMP-2 and -9 resulted in degradation of extracellular matrix and destruction of basilar membrane, which facilitated the migration of cancer cells (26,27). On the contrary, restricted expression of MMP-2 and -9 in cancer cells leads to a better prognosis (28)(29)(30). The results from the present study showed that exposure of NSCLC H520 cells to phloretin led to decreased invasion and migratory ability.…”

Section: Discussionsupporting

confidence: 55%

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases

Wang

Nan

et al. 2015

International Journal of Oncology

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Abstract. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases and the prognosis of NSCLC patients is unsatisfactory since 5-year survival rate of NSCLC is still as low as 11%. Natural compounds derived from plants with few or no side effects have been recognized as alternative or auxiliary cure for cancer patients. Phloretin is such an agent possessing various pharmacological activities; however, there is scarce information on its anticancer effects on NSCLC. It was evaluated and confirmed, in the present study, that phloretin inhibited proliferation and induced apoptosis in A549, Calu-1, H838 and H520 cells in a dosedependent manner, phloretin also suppressed the invasion and migration of NSCLC cells. We further confirmed that phloretin dose-dependently suppressed the expression of Bcl-2, increased the protein expression of cleaved-caspase-3 and -9, and deregulated the expression of matrix metalloproteinases (MMP)-2 and -9 on gene and protein levels. Besides, evaluations revealed that phloretin enhanced the anticancer effects of cisplatin on inhibition of proliferation and induction of apoptosis in NSCLC cells. Moreover, phloretin facilitated the effects of cisplatin on deregulation of Bcl-2, MMP-2 and -9, and upregulation of cleaved-caspase-3 and -9. In conclusion, the present study demonstrated that phloretin possessed anticancer effects and enhanced the anticancer effects of cisplatin on NSCLC cell lines by suppressing proliferation, inducing apoptosis and inhibiting invasion and migration of the cells through regulating apoptotic pathways and MMPs. IntroductionLung cancer is the most frequent reason for cancer related death and non-small cell lung cancer (NSCLC) accounts for ~80-85% of all lung cancer cases (1). Although there has been notable progression in combination chemotherapy and surgical techniques, the prognosis of NSCLC patients is still unsatisfactory since 5-year survival rate of NSCLC with all stages and histological types is as low as 11% (2). Besides the prolonged life time, the survival quality of NSCLC patients should also be taken care of, while the high toxicity of anticancer drugs adopted in clinical first line to normal tissues and cells is an impassable barrier for cancer therapy and a heavy burden for patients to bear. It would be better if there were some methods that could improve the clinical therapy effects and relieve the pain of the patients.Agents derived from various plants with few or no side effects have been recognized as potential alternative or auxiliary cure for cancer patients. Flavonoids, one major class of polyphenols, are well known for their antioxidant activity by eliminating reactive oxygen species (3) and chelating metal atoms (4,5). There is also substantial research suggesting that flavonoids have anticancer effects (6). Phloretin [3-(4-hydroxyphenyl)-1-(2,4,5-trihydroxyphenyl)] is one of the major phenolic flavonoid glucosides (structure showed in Fig. 1) found in apples and other plants, such as Pieris japonica, Hoveniae Lignum and...

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“…In addition to lung cancer, other cancers such as breast cancer exhibit high expression of MMP9 (38)(39)(40). MMP9 is associated with pathological type, and positive immunostaining for MMP9 has prognostic value for the distant metastasis or local recurrence of lung cancer (17,41,42). VEGF has been reported to induce tumor blood vessel proliferation and possibly contributes to the extravasation of cancer cells and the formation of metastasis (43).…”

Section: Discussionmentioning

confidence: 99%

ARHGAP6 regulates the proliferation, migration and invasion of lung cancer cells

et al. 2019

Oncol Rep

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Lung cancer, a leading cause of cancer-related deaths, is frequently diagnosed in both males and females worldwide. In the present study, the Ras homologue GTPase activation protein 6 (ARHGAP6), which belongs to the Rho GTPase-activating protein (RhoGAP) family, was found to have low expression in tumor tissues from patients with lung cancer, accompanied by high expression of matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF). In A549 and H1299 cells, upregulation of ARHGAP6 inhibited tumor growth and metastasis and reduced the levels of MMP9, VEGF and p-STAT3, while the levels STAT3 were unchanged, as demonstrated by CCK-8, migration and invasion assays as well as western blot analysis. In addition, interleukin 6 (IL-6)-induced migration, invasion and MMP9 and VEGF expression, and STAT3 signaling activity were suppressed by ARHGAP6 upregulation. Based on these data, we concluded that ARHGAP6 is critically important in lung cancer progression and that upregulation of ARHGAP6 benefits the treatment and prevention of lung cancer, possibly through the suppression of MMP9, VEGF and STAT3 signaling activation.

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Matrix Metalloproteinase-9 Expression in Lung Cancer Patients and Its Relation to Serum MMP-9 Activity, Pathologic Type, and Prognosis

Cited by 62 publications

References 23 publications

Blood test shows high accuracy in detecting stage I non-small cell lung cancer

Blood test shows high accuracy in detecting stage I non-small cell lung cancer

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases

ARHGAP6 regulates the proliferation, migration and invasion of lung cancer cells

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