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Tumor Microenvironment Varies under Different TCM ZHENG Models and Correlates with Treatment Response to Herbal Medicine.

Chen Z, Chen LY, Wang P, Dai HY, Gao S, Wang K - Evid Based Complement Alternat Med (2012)

Bottom Line: In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG.We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5.The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

ABSTRACT
In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer.

No MeSH data available.


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Correlation between microenvironment and tumor growth under different ZHENG conditions. (a) The levels of CAF- and TAM-derived secreted cytokines, SDF-1 and CCL5, in tumor from the Shi-Re, Pi-Xu, and Xue-Yu ZHENG models were evaluated with ELISA assay. Data are expressed as the mean ± SE. (b and c) IHC staining for CXCR4 and CCR5 on sections of tumors from ZHENG models was performed and representative photos are shown in (b). The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG are shown in (c). (d) Effect of ZHENG on tumor growth in a subcutaneously transplanted tumor model. Xenograft tumor model combined with ZHENG model was established as described in Figure 2(a). Mean volumes of tumors from each group were measured. Mean ± standard deviation was determined for 10 mice in each group.
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fig3: Correlation between microenvironment and tumor growth under different ZHENG conditions. (a) The levels of CAF- and TAM-derived secreted cytokines, SDF-1 and CCL5, in tumor from the Shi-Re, Pi-Xu, and Xue-Yu ZHENG models were evaluated with ELISA assay. Data are expressed as the mean ± SE. (b and c) IHC staining for CXCR4 and CCR5 on sections of tumors from ZHENG models was performed and representative photos are shown in (b). The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG are shown in (c). (d) Effect of ZHENG on tumor growth in a subcutaneously transplanted tumor model. Xenograft tumor model combined with ZHENG model was established as described in Figure 2(a). Mean volumes of tumors from each group were measured. Mean ± standard deviation was determined for 10 mice in each group.

Mentions: CAFs stimulate tumor cell proliferation and invasion through various growth factors, hormones, and cytokines [13]. SDF-1 is a CAF-derived chemokine that has been shown to directly boost the proliferation and invasion of pancreatic cancer cells [14]. Thus, we evaluated the levels of secreted SDF-1 in tumors under different ZHENG conditions, and the expression of CXCR4, the SDF-1 cognate receptor, in tumor cells. The results of ELISA assays showed decreased levels of SDF-1 released in tumors in the Shi-Re and Pi-Xu groups compared to the control mice. This was not observed in the Xue-Yu tumors (Figure 3(a)). This result was consistent with the observation that the Shi-Re and Pi-Xu tumors exhibited decreased CAF proliferative activity. However, there was no difference in CXCR4 expression among the ZHENG models and control tumor cells (Figures 3(b) and 3(c)).


Tumor Microenvironment Varies under Different TCM ZHENG Models and Correlates with Treatment Response to Herbal Medicine.

Chen Z, Chen LY, Wang P, Dai HY, Gao S, Wang K - Evid Based Complement Alternat Med (2012)

Correlation between microenvironment and tumor growth under different ZHENG conditions. (a) The levels of CAF- and TAM-derived secreted cytokines, SDF-1 and CCL5, in tumor from the Shi-Re, Pi-Xu, and Xue-Yu ZHENG models were evaluated with ELISA assay. Data are expressed as the mean ± SE. (b and c) IHC staining for CXCR4 and CCR5 on sections of tumors from ZHENG models was performed and representative photos are shown in (b). The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG are shown in (c). (d) Effect of ZHENG on tumor growth in a subcutaneously transplanted tumor model. Xenograft tumor model combined with ZHENG model was established as described in Figure 2(a). Mean volumes of tumors from each group were measured. Mean ± standard deviation was determined for 10 mice in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Correlation between microenvironment and tumor growth under different ZHENG conditions. (a) The levels of CAF- and TAM-derived secreted cytokines, SDF-1 and CCL5, in tumor from the Shi-Re, Pi-Xu, and Xue-Yu ZHENG models were evaluated with ELISA assay. Data are expressed as the mean ± SE. (b and c) IHC staining for CXCR4 and CCR5 on sections of tumors from ZHENG models was performed and representative photos are shown in (b). The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG are shown in (c). (d) Effect of ZHENG on tumor growth in a subcutaneously transplanted tumor model. Xenograft tumor model combined with ZHENG model was established as described in Figure 2(a). Mean volumes of tumors from each group were measured. Mean ± standard deviation was determined for 10 mice in each group.
Mentions: CAFs stimulate tumor cell proliferation and invasion through various growth factors, hormones, and cytokines [13]. SDF-1 is a CAF-derived chemokine that has been shown to directly boost the proliferation and invasion of pancreatic cancer cells [14]. Thus, we evaluated the levels of secreted SDF-1 in tumors under different ZHENG conditions, and the expression of CXCR4, the SDF-1 cognate receptor, in tumor cells. The results of ELISA assays showed decreased levels of SDF-1 released in tumors in the Shi-Re and Pi-Xu groups compared to the control mice. This was not observed in the Xue-Yu tumors (Figure 3(a)). This result was consistent with the observation that the Shi-Re and Pi-Xu tumors exhibited decreased CAF proliferative activity. However, there was no difference in CXCR4 expression among the ZHENG models and control tumor cells (Figures 3(b) and 3(c)).

Bottom Line: In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG.We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5.The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

ABSTRACT
In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus