Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer
Aim: To evaluate concentration of MMP-9 in blood plasma and broncho-alveolar lavage fluid (BALF) from patients with non-small cell lung cancer (NSCLC). Methods: Blood рlasma from 40 NSCLC patients and 40 healthy donors was collected and concentrations of blood plasma and BALF MMP-9 were measured usi...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2006
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| Цитувати: | Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer / G. Bugdayci, T. Kaplan, S. Sezer, T. Turhan, Y. Koca, B. Kocer, E. Yildirim // Experimental Oncology. — 2006. — Т. 28, № 2. — С. 169-171. — Бібліогр.: 16 назв. — англ. |
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irk-123456789-1375632018-06-18T03:07:30Z Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer Bugdayci, G. Kaplan, T. Sezer, S. Turhan, T. Koca, Y. Kocer, B. Yildirim, E. Short communications Aim: To evaluate concentration of MMP-9 in blood plasma and broncho-alveolar lavage fluid (BALF) from patients with non-small cell lung cancer (NSCLC). Methods: Blood рlasma from 40 NSCLC patients and 40 healthy donors was collected and concentrations of blood plasma and BALF MMP-9 were measured using ELISA. Correlation between MMP-9 level and gender, histological type of tumor and stage of disease was analyzed. Results: Levels of blood plasma MMP-9 were significantly higher in NSCLC patients (p < 0.0001) then in control group, and were especially high in patients with stage IV of disease (stage I vs stage IV — p < 0.005, stage II vs stage IV — p < 0.01, stage III vs stage IV — p < 0.01). Also, stage IV of NSCLC was characterized by the highest level of BALF MMP-9 (stage I vs stage IV — p < 0.002, stage II vs stage IV p < 0.002, and stage III vs stage IV p < 0.007). Correlation between blood plasma and BALF MMP-9 levels and gender or histological type of tumor was insignificant. Conclusion: Our data revealed significant correlation between tumor stage and BALF and plasma MMP-9 levels in NSCLC patients. Цель: определить концентрацию матриксной металлопротеиназы 9 (ММП-9) в плазме крови и бронхо-альвеолярной жидкости (БАЖ) больных немелкоклеточным раком легкого (НМКРЛ). Методы: концентрацию ММП-9 в плазме крови и БАЖ больных НМКРЛ (n = 40) и здоровых доноров (n = 40) определяли иммуноферментным методом и анализировали корреляцию этих параметров с клиническими данными (полом больного, гистологическим типом опухоли, стадией заболевания). Результаты: содержание ММП-9 в плазме крови было значительно выше у больных НМКРЛ по сравнению с контрольной группой (p < 0,0001), особенно у больных с IV стадией заболевания. Стадия IV НМКРЛ также характеризовалась наиболее высоким уровнем ММП-9 в БАЖ. Корреляции между уровнем ММП-9 в плазме крови и БАЖ, полом больного и гистологическим типом опухоли не была выявлена. Выводы: существует статистически значимая корреляция между стадией развития НМКРЛ и содержанием ММП-9 в плазме крови и БАЖ больных. 2006 Article Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer / G. Bugdayci, T. Kaplan, S. Sezer, T. Turhan, Y. Koca, B. Kocer, E. Yildirim // Experimental Oncology. — 2006. — Т. 28, № 2. — С. 169-171. — Бібліогр.: 16 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137563 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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English |
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Short communications Short communications |
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Short communications Short communications Bugdayci, G. Kaplan, T. Sezer, S. Turhan, T. Koca, Y. Kocer, B. Yildirim, E. Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer Experimental Oncology |
| description |
Aim: To evaluate concentration of MMP-9 in blood plasma and broncho-alveolar lavage fluid (BALF) from patients with non-small cell lung cancer (NSCLC). Methods: Blood рlasma from 40 NSCLC patients and 40 healthy donors was collected and concentrations of blood plasma and BALF MMP-9 were measured using ELISA. Correlation between MMP-9 level and gender, histological type of tumor and stage of disease was analyzed. Results: Levels of blood plasma MMP-9 were significantly higher in NSCLC patients (p < 0.0001) then in control group, and were especially high in patients with stage IV of disease (stage I vs stage IV — p < 0.005, stage II vs stage IV — p < 0.01, stage III vs stage IV — p < 0.01). Also, stage IV of NSCLC was characterized by the highest level of BALF MMP-9 (stage I vs stage IV — p < 0.002, stage II vs stage IV p < 0.002, and stage III vs stage IV p < 0.007). Correlation between blood plasma and BALF MMP-9 levels and gender or histological type of tumor was insignificant. Conclusion: Our data revealed significant correlation between tumor stage and BALF and plasma MMP-9 levels in NSCLC patients. |
| format |
Article |
| author |
Bugdayci, G. Kaplan, T. Sezer, S. Turhan, T. Koca, Y. Kocer, B. Yildirim, E. |
| author_facet |
Bugdayci, G. Kaplan, T. Sezer, S. Turhan, T. Koca, Y. Kocer, B. Yildirim, E. |
| author_sort |
Bugdayci, G. |
| title |
Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer |
| title_short |
Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer |
| title_full |
Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer |
| title_fullStr |
Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer |
| title_full_unstemmed |
Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer |
| title_sort |
matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2006 |
| topic_facet |
Short communications |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/137563 |
| citation_txt |
Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer / G. Bugdayci, T. Kaplan, S. Sezer, T. Turhan, Y. Koca, B. Kocer, E. Yildirim // Experimental Oncology. — 2006. — Т. 28, № 2. — С. 169-171. — Бібліогр.: 16 назв. — англ. |
| series |
Experimental Oncology |
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2025-07-10T02:35:15Z |
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2025-07-10T02:35:15Z |
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1837225651723042816 |
| fulltext |
Experimental Oncology ���� ��������� ���� ���ne�� ������� ��������� ���� ���ne�� ��� ���
Metalloproteinases �MMPs�� are gro�p of enzymes
that play significant role in the metabolism of extracell�lar
matrix components�� tiss�e repair and cell migration [�].
MMPs are secreted in inactive form from different kind
of cells or are expressed as plasma membrane bo�nd
form. MMPs play important roles in t�mor invasion and
metastasis and are also involved in initial stages of t�mor
development by reg�lating cell proliferation�� apoptosis��
angiogenesis and imm�ne s�rveillance [��� 3]. Matrix
metalloproteinase-� �MMP-��� belongs to the family of
gelatinases that occ�py special position beca�se of their
ability to degrade both elastin and type IV collagen — ma-
jor component of basal membrane [4�� 5].
L�ng cancer�� the leading cancer type in the developed
co�ntries�� has been widely investigated for its etiological
factors. Some nat�ral genetic variations have been as-
sociated with individ�al s�sceptibility to this t�mor [��� �].
More than one million new ca�ses of l�ng cancer occ�r in
the world every year. Non-small cell l�ng cancer �NSCLC��
acco�nts more than �5% of l�ng cancers.
Elevation of MMP-� level associated with metas-
tasis and with decrease of s�rvival time�� has been
reported [����]. The aim of this st�dy was to inves-
tigate the interaction between the levels of MMP-�
in broncho-alveolar lavage fl�id �BALF�� and plasma
of patients with NSCLC and to analize correlation bet-
ween these indices and t�mor stage.
Blood plasma samples from 4� healthy donors
��� males and �� females�� and 4� NSCLC patients �3�
males and � females�� c�red in Ankara N�m�ne Teach-
ing and Research Hospital �T�rkey�� from March ���4
to April ���5�� were st�died. The mean age of NSCLC
patients and controls was 5� ± �.3 years �range 3������
and 54 ± ��.� years �range 34������� respectively. Based
on the WHO criteria�� the patients gro�p consisted of
�4 patients with adenocarcinoma and �� with sq�a-
mo�s cell carcinoma. Nineteen patients had early
stage of disease �� patients with stage I and �3 patients
with stage II���� �3 patients had locally advanced disease
�stage III���� � patients were at stage IV. All patients were
staged at the time of s�rgery following the g�idelines
of the American �oint Committee on Cancer Stag-
ing [��]. The proced�re incl�ded chest radiography��
comp�ter tomography �CT�� scans of the chest and
abdomen�� magnetic resonance imaging of the brain
and bone scanning. Local ethical committee approved
all protocols for this st�dy. Patients with NSCLC and
healthy donors were smokers. Clinical parameters of
patients are s�mmarized in Table �.
Table 1. Clinicopathologic parameters of patients with NSCLC
Parameters NSCLC patients (n = 40)
Age (years)
Mean
Range
56 ± 8.3
31–71
Gender
Male
Female
32
8
Histological Type
Adenocarcinoma
Squamous cell carcinoma
14
26
Stage
IA
IB
IIA
IIB
IIIA
IIIB
IV
1
5
4
9
9
4
8
BALF were collected only from the gro�p of pa-
tients with NSCLC. Veno�s blood samples obtained
from NSCLC patients and donors were placed in t�bes
containing EDTA�� immediately centrif�ged ��5�� g x
�� min��. BALF and plasma were stored in aliq�ots at
��� °C �ntil �se.
MATRIX METALLOPROTEINASE-9 IN BRONCHO-ALVEOLAR LAVAGE
FLUID OF PATIENTS WITH NON-SMALL CELL LUNG CANCER
G. Bugdayci1, *, T. Kaplan2, S. Sezer3, T. Turhan3, Y. Koca3, B. Kocer3, E. Yildirim2
1Department of Biochemistry, Izzet Baysal School of Medicine, Abant Izzet Baysal University, Bolu, Turkey
2Department of Thoracic Surgery, Ankara Numune Teaching and Research Hospital, Ankara, Turkey
3Department of Biochemistry, Ankara Numune Teaching and Research Hospital, Ankara, Turkey
Aim: To evaluate concentration of MMP-9 in blood plasma and broncho-alveolar lavage fluid (BALF) from patients with non-small
cell lung cancer (NSCLC). Methods: Blood рlasma from 40 NSCLC patients and 40 healthy donors was collected and concentrations
of blood plasma and BALF MMP-9 were measured using ELISA. Correlation between MMP-9 level and gender, histological type of
tumor and stage of disease was analyzed. Results: Levels of blood plasma MMP-9 were significantly higher in NSCLC patients (p <
0.0001) then in control group, and were especially high in patients with stage IV of disease (stage I vs stage IV — p < 0.005, stage II
vs stage IV — p < 0.01, stage III vs stage IV — p < 0.01). Also, stage IV of NSCLC was characterized by the highest level of BALF
MMP-9 (stage I vs stage IV — p < 0.002, stage II vs stage IV p < 0.002, and stage III vs stage IV p < 0.007). Correlation between
blood plasma and BALF MMP-9 levels and gender or histological type of tumor was insignificant. Conclusion: Our data revealed
significant correlation between tumor stage and BALF and plasma MMP-9 levels in NSCLC patients.
Key Words: matrix metalloproteinase-9, plasma, broncho-alveolar lavage, nonsmall cell lung cancer, metastasis, histological type.
Received: May 11, 2006.
*Correspondence: Fax: 0090 374 253 46 15
E-mail: gbugdayci@gmail.com
bugdayci_g@ibu.edu.tr
Abbreviations used: BALF – broncho-alveolar lavage fluid; MMP-9 –
matrix metalloproteinase-9; NSCLC – non-small cell lung cancer.
Exp Oncol ����
���� ��� �������
��� Experimental Oncology ���� ��������� ���� ���ne��
ELISA was performed to detect MMP-� in ser�m and
BALF samples�� �sing Q�antikine kits �R & D Systems
Inc.�� Minneapolis�� USA�� and specific antibodies by
ro�tine proced�re. The optical density was detected
�sing Tecan S�nrise Elisa Microplate Reader �UK�� at
wave length of 45� nm. Each sample was assayed in
d�plicate and val�es were within the linear portion of the
standard c�rve. The minim�m detectable concentration
was less than �.�5� ng/ml.
Val�es were expressed as Mean ± SE. The dif-
ference between gro�ps was eval�ated by St�dents
t-test. The difference between stages was meas�red
by Kr�skall-Wallis and than Mann Whitney U-test. For
correlation analysis Pearsons test was �sed. The dif-
ference was considered significant if p < �.��.
The plasma MMP-� level of NSCLC patients
����.�� ± ���.�� ng/ml�� was significantly higher than in
control gro�p ����.�� ± ��.�� ng/ml�� p < ���������. Level
of BALF MMP-� was determined in NSCLC patients
��55.�� ± ���.3� ng/ml��. Level of plasma MMP-� from
patients with stage IV was significantly higher than in
controls �Table ���.
Table 2. Levels of plasma and BALF MMP-9 in patients with NSCLC.
Sex F/M Hystologic
Type A/S
Plasma MMP-9
ng/ml BALF MMP-9 ng/ml
Stage I 1/5 1/5 176.5 ± 90.95* 412.17 ± 108.84**
Stage II 4/9 5/8 198.38 ± 86.98 636.15 ± 334.45
Stage III 3/10 6/7 211.69 ± 83.11 780.34 ± 387.71
Stage IV 0/8 2/6 560.62 ± 220.25* 1667.62 ± 754.04**
Control 11/29 — 118.80 ± 97.17 —
Female/Male F/M, Adenocarcinoma/Squamous cell carcinoma A/S
*p < 0.005 stage I–IV plasma MMP-9 levels
**p < 0.002 stage I–IV BALF MMP-9 levels
Plasma and BALF MMP-� levels in stages I patients
were significantly lower than these in stages IV patients
�p < �.��� and p < �.��5�� respectively��. MMP-� levels in
BALF were similar at early stages�� b�t that in stage IV was
characterized by the highest level of BALF and plasma
MMP-� levels �stage I vs stage IV — p < �.����� stage II vs
stage IV — p < �.����� and stage III vs stage IV — p < �.���
for BALF; stage I vs IV — p < �.��5�� stage II vs IV — p < �.����
and stage III vs IV — p < �.�� for plasma MMP-���.
The correlation between MMP-� level in blood
plasma or BALF and the stage of disease was fo�nd
significant �Pearson’s r = �.��� �p < �.�������� Pear-
son’s r = �.�3� �p < �.������ respectively��. However��
no correlation between plasma or BALF MMP-� levels
and gender �r = �.�3� for plasma�� r = �.3�� for BALF��
p > �.�5���� or histological type of t�mor �r = �.��� for
plasma�� r = �.��� for BALF�� has been revealed.
So�� o�r st�dy has demonstrated the significant in-
crease of plasma MMP-� level in NSCLC patients com-
pared to healthy donors. This finding is in accordance with
the data of other a�thors [��� ���� �3�� �4] reporting on eleva-
tion of plasma or ser�m MMP-� levels in NSCLC patients.
In agreement with previo�s reports [�5�� ��]�� o�r res�lts
showed that MMP-� levels do not depend significantly on
patient’s gender or/and histological type of t�mor.
We report for the first time an association between
BALF MMP-� levels and stage of NSCLC. The levels
of BALF MMP-� are increased �pon advanced l�ng
cancer�� however the mechanisms responsible for the
elevation of MMP-� levels remain �nclear. F�rther
st�dies on a larger n�mber of patients are req�ired to
explore the prognostic val�es for these metastasis-
associated markers for NSCLC.
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Experimental Oncology ���� ��������� ���� ���ne�� ������� ��������� ���� ���ne�� ��� ���
Содержание матрикСной метаЛЛоПротеинаЗЫ 9
в БронХоаЛЬвеоЛЯрной жидкоСти БоЛЬнЫХ
немеЛкокЛетоЧнЫм раком ЛеГкоГо
Цель: определить концентрацию матриксной металлопротеиназы 9 (ММП-9) в плазме крови и бронхо-альвеолярной
жидкости (БАЖ) больных немелкоклеточным раком легкого (НМКРЛ). Методы: концентрацию ММП-9 в плазме крови
и БАЖ больных НМКРЛ (n �� 40) и здоровых доноров (n �� 40) определяли имм�но�ерментным методом и анализировалиn �� 40) и здоровых доноров (n �� 40) определяли имм�но�ерментным методом и анализировали �� 40) и здоровых доноров (n �� 40) определяли имм�но�ерментным методом и анализировалиn �� 40) определяли имм�но�ерментным методом и анализировали �� 40) определяли имм�но�ерментным методом и анализировали
корреляцию этих параметров с клиническими данными (полом больного, гистологическим типом оп�холи, стадией забо-
левания). Результаты: содержание ММП-9 в плазме крови было значительно выше � больных НМКРЛ по сравнению с
контрольной гр�ппой (p < 0,0001), особенно � больных с IV стадией заболевания. �тадия IV НМКРЛ также характери-IV стадией заболевания. �тадия IV НМКРЛ также характери- стадией заболевания. �тадия IV НМКРЛ также характери-IV НМКРЛ также характери- НМКРЛ также характери-
зовалась наиболее высоким �ровнем ММП-9 в БАЖ. Корреляции межд� �ровнем ММП-9 в плазме крови и БАЖ, полом
больного и гистологическим типом оп�холи не была выявлена. Выводы: с�ществ�ет статистически значимая корреляция
межд� стадией развития НМКРЛ и содержанием ММП-9 в плазме крови и БАЖ больных.
Ключевые слова: матриксная металлопротеиназа 9, плазма крови, бронхо-альвеолярная жидкость, немелкоклеточный
рак легкого, метастазы, гистологический тип оп�холи.
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