Abstract
Menstrual cycle activity predisposes to ovarian epithelial tumors based on numerous epidemiological studies. We showed that the hormones involved in menstrual cycle regulation modulate cell cycle activity in these tumors in an accompanying paper. We investigated whether such hormones could also influence angiogenesis, an important determinant of tumor progression, in the same tumors. Treatment with progesterone (P4) stimulated VEGF protein secretion in 4 of 5 ovarian carcinoma cell lines examined. Northern blot analyses performed in MCV50 cells showed that this effect was accompanied by increased VEGF mRNA levels. P4 also stimulated VEGF promoter activity in these cells. Estradiol (E2) showed a similar, but substantially smaller effect on VEGF secretion which was additive to that of P4. Conditioned medium from P4-treated cells strongly stimulated angiogenesis on chicken chorio-allantoic membranes. Incubating the conditioned medium with a neutralizing anti-VEGF antibody, but not with non-specific immunoglobulins abolished this effect. Angiogenic activity was not altered by treatment of the membranes with P4 directly. We conclude that P4 can stimulate angiogenic activity via induction of VEGF secretion in some ovarian epithelial tumors. Therapeutic use of progestins may be most effective when administered in combination with an anti-angiogenic agent, at least against a subset of ovarian carcinomas.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 307-312 |
| Number of pages | 6 |
| Journal | Cancer Biology and Therapy |
| Volume | 1 |
| Issue number | 3 |
| State | Published - May 2002 |
| Externally published | Yes |
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Keywords
- Angiogenesis
- Hormones
- Menstrual cycle
- Ovarian neoplasia
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Molecular Medicine
- Pharmacology
Cite this
Effect of reproductive hormones on ovarian epithelial tumors : II. Effect on angiogenic activity. / Chen, Chen; Petitclerc, Eric; Zhou, Hong; Brooks, Peter C.; Sun, Tong; Yu, Mimi C.; Zheng, Wenxin -; Dubeau, Louis.
In: Cancer Biology and Therapy, Vol. 1, No. 3, 05.2002, p. 307-312.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of reproductive hormones on ovarian epithelial tumors
T2 - II. Effect on angiogenic activity
AU - Chen, Chen
AU - Petitclerc, Eric
AU - Zhou, Hong
AU - Brooks, Peter C.
AU - Sun, Tong
AU - Yu, Mimi C.
AU - Zheng, Wenxin -
AU - Dubeau, Louis
PY - 2002/5
Y1 - 2002/5
N2 - Menstrual cycle activity predisposes to ovarian epithelial tumors based on numerous epidemiological studies. We showed that the hormones involved in menstrual cycle regulation modulate cell cycle activity in these tumors in an accompanying paper. We investigated whether such hormones could also influence angiogenesis, an important determinant of tumor progression, in the same tumors. Treatment with progesterone (P4) stimulated VEGF protein secretion in 4 of 5 ovarian carcinoma cell lines examined. Northern blot analyses performed in MCV50 cells showed that this effect was accompanied by increased VEGF mRNA levels. P4 also stimulated VEGF promoter activity in these cells. Estradiol (E2) showed a similar, but substantially smaller effect on VEGF secretion which was additive to that of P4. Conditioned medium from P4-treated cells strongly stimulated angiogenesis on chicken chorio-allantoic membranes. Incubating the conditioned medium with a neutralizing anti-VEGF antibody, but not with non-specific immunoglobulins abolished this effect. Angiogenic activity was not altered by treatment of the membranes with P4 directly. We conclude that P4 can stimulate angiogenic activity via induction of VEGF secretion in some ovarian epithelial tumors. Therapeutic use of progestins may be most effective when administered in combination with an anti-angiogenic agent, at least against a subset of ovarian carcinomas.
AB - Menstrual cycle activity predisposes to ovarian epithelial tumors based on numerous epidemiological studies. We showed that the hormones involved in menstrual cycle regulation modulate cell cycle activity in these tumors in an accompanying paper. We investigated whether such hormones could also influence angiogenesis, an important determinant of tumor progression, in the same tumors. Treatment with progesterone (P4) stimulated VEGF protein secretion in 4 of 5 ovarian carcinoma cell lines examined. Northern blot analyses performed in MCV50 cells showed that this effect was accompanied by increased VEGF mRNA levels. P4 also stimulated VEGF promoter activity in these cells. Estradiol (E2) showed a similar, but substantially smaller effect on VEGF secretion which was additive to that of P4. Conditioned medium from P4-treated cells strongly stimulated angiogenesis on chicken chorio-allantoic membranes. Incubating the conditioned medium with a neutralizing anti-VEGF antibody, but not with non-specific immunoglobulins abolished this effect. Angiogenic activity was not altered by treatment of the membranes with P4 directly. We conclude that P4 can stimulate angiogenic activity via induction of VEGF secretion in some ovarian epithelial tumors. Therapeutic use of progestins may be most effective when administered in combination with an anti-angiogenic agent, at least against a subset of ovarian carcinomas.
KW - Angiogenesis
KW - Hormones
KW - Menstrual cycle
KW - Ovarian neoplasia
UR - http://www.scopus.com/inward/record.url?scp=1842837164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842837164&partnerID=8YFLogxK
M3 - Article
C2 - 12432284
AN - SCOPUS:1842837164
VL - 1
SP - 307
EP - 312
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
SN - 1538-4047
IS - 3
ER -