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Tumor interstitial fluid and gastric cancer metastasis: An experimental study to verify the hypothesis of “tumor-phlegm microenvironment”

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Abstract

Objective

To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to “muddy phlegm” in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.

Methods

An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups.

Results

There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups.

Conclusions

TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of “tumor-phlegm microenvironment”.

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Author information

Authors and Affiliations

  1. Institute of Traditional Chinese Medicine Research, Chinese People’s Liberation Army General Hospital, Beijing, 100853, China

    Da-zhi Sun  (孙大志) & Ming-hui Yang  (杨明会)

  2. Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Da-zhi Sun  (孙大志), Jian-peng Jiao  (矫健鹏), Da-wei Ju  (巨大维), Min Ye  (叶 敏), Xuan Zhang  (张 璇), Jing-yu Xu  (徐晶钰), Ye Lu  (陆 烨) & Pin-kang Wei  (魏品康)

  3. Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Jin He  (何 金)

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  1. Da-zhi Sun  (孙大志)
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  2. Jian-peng Jiao  (矫健鹏)
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  4. Min Ye  (叶 敏)
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  7. Ye Lu  (陆 烨)
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  8. Jin He  (何 金)
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  9. Pin-kang Wei  (魏品康)
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  10. Ming-hui Yang  (杨明会)
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Corresponding authors

Correspondence to Pin-kang Wei  (魏品康) or Ming-hui Yang  (杨明会).

Additional information

Supported by the Major Research Program Grant of the National Science Foundation (No. 90709044), and China Postdoctoral Science Foundation Project (No. 20100480096)

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Sun, Dz., Jiao, Jp., Ju, Dw. et al. Tumor interstitial fluid and gastric cancer metastasis: An experimental study to verify the hypothesis of “tumor-phlegm microenvironment”. Chin. J. Integr. Med. 18, 350–358 (2012). https://doi.org/10.1007/s11655-012-1085-z

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  • DOI: https://doi.org/10.1007/s11655-012-1085-z

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