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Aerosol delivery of small hairpin osteopontin blocks pulmonary metastasis of breast cancer in mice.

Yu KN, Minai-Tehrani A, Chang SH, Hwang SK, Hong SH, Kim JE, Shin JY, Park SJ, Kim JH, Kwon JT, Jiang HL, Kang B, Kim D, Chae CH, Lee KH, Yoon TJ, Beck GR, Cho MH - PLoS ONE (2010)

Bottom Line: Thus, a novel approach to prevent breast tumor metastasis is needed.Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.

ABSTRACT

Background: Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed.

Methodology/principal finding: Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.

Conclusion/significance: Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.

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Related in: MedlinePlus

Effect of Aerosol-delivered shOPN on expression level of PCNA.(A) Western blot of PCNA. (B) Densitometric analysis of PCNA. (C) Immunohistochemical analysis of PCNA. Magnification: ×400. Scale bar: 20 µm. (D) Comparison of PCNA labeling index. Each bar represents the mean± S.E.M (n = 3). *Statistically different (P<0.05) compared to control group. **Statistically different (P<0.01) compared to control group. #Statistically different (P<0.05) compared to scrambled control. ##Statistically different (P<0.01) compared to scrambled control.
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pone-0015623-g004: Effect of Aerosol-delivered shOPN on expression level of PCNA.(A) Western blot of PCNA. (B) Densitometric analysis of PCNA. (C) Immunohistochemical analysis of PCNA. Magnification: ×400. Scale bar: 20 µm. (D) Comparison of PCNA labeling index. Each bar represents the mean± S.E.M (n = 3). *Statistically different (P<0.05) compared to control group. **Statistically different (P<0.01) compared to control group. #Statistically different (P<0.05) compared to scrambled control. ##Statistically different (P<0.01) compared to scrambled control.

Mentions: Expression of proliferating cell nuclear antigen (PCNA) is increased in several types of cancers. Moreover, it has been postulated as a useful prognostic parameter for certain cancers [24]. Therefore, we determined the expression level of PCNA by Western blot analysis, which revealed that aerosol-delivered shOPN decreased PCNA expression in the lung of breast cancer model mice (Fig. 4A). Densitometric analysis further confirmed the Western blot results (Fig. 4B). Furthermore, IHC analysis showed that aerosol-delivered shOPN significantly decreased the expression level of PCNA compared to the control and scrambled group (Fig. 4C). The relative staining intensity also clearly confirmed this (Fig. 4D).


Aerosol delivery of small hairpin osteopontin blocks pulmonary metastasis of breast cancer in mice.

Yu KN, Minai-Tehrani A, Chang SH, Hwang SK, Hong SH, Kim JE, Shin JY, Park SJ, Kim JH, Kwon JT, Jiang HL, Kang B, Kim D, Chae CH, Lee KH, Yoon TJ, Beck GR, Cho MH - PLoS ONE (2010)

Effect of Aerosol-delivered shOPN on expression level of PCNA.(A) Western blot of PCNA. (B) Densitometric analysis of PCNA. (C) Immunohistochemical analysis of PCNA. Magnification: ×400. Scale bar: 20 µm. (D) Comparison of PCNA labeling index. Each bar represents the mean± S.E.M (n = 3). *Statistically different (P<0.05) compared to control group. **Statistically different (P<0.01) compared to control group. #Statistically different (P<0.05) compared to scrambled control. ##Statistically different (P<0.01) compared to scrambled control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3008732&req=5

pone-0015623-g004: Effect of Aerosol-delivered shOPN on expression level of PCNA.(A) Western blot of PCNA. (B) Densitometric analysis of PCNA. (C) Immunohistochemical analysis of PCNA. Magnification: ×400. Scale bar: 20 µm. (D) Comparison of PCNA labeling index. Each bar represents the mean± S.E.M (n = 3). *Statistically different (P<0.05) compared to control group. **Statistically different (P<0.01) compared to control group. #Statistically different (P<0.05) compared to scrambled control. ##Statistically different (P<0.01) compared to scrambled control.
Mentions: Expression of proliferating cell nuclear antigen (PCNA) is increased in several types of cancers. Moreover, it has been postulated as a useful prognostic parameter for certain cancers [24]. Therefore, we determined the expression level of PCNA by Western blot analysis, which revealed that aerosol-delivered shOPN decreased PCNA expression in the lung of breast cancer model mice (Fig. 4A). Densitometric analysis further confirmed the Western blot results (Fig. 4B). Furthermore, IHC analysis showed that aerosol-delivered shOPN significantly decreased the expression level of PCNA compared to the control and scrambled group (Fig. 4C). The relative staining intensity also clearly confirmed this (Fig. 4D).

Bottom Line: Thus, a novel approach to prevent breast tumor metastasis is needed.Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.

ABSTRACT

Background: Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed.

Methodology/principal finding: Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.

Conclusion/significance: Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.

Show MeSH
Related in: MedlinePlus