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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.


Related in: MedlinePlus

Alterations of tumor microenvironments under different ZHENG conditions. (a) Xenograft tumor models were established as described. On the next day, three types of ZHENG, namely, Shi-Re, Pi-Xu, and Xue-Yu were established. Tumors were obtained 4 wks after implantation. IHC staining for vimentin and α-SMA on sections of tumors was performed for evaluating CAF proliferative activities (top). IHC staining for CD68 was performed for evaluating TAM infiltration (low). Original magnification, 200x. (b) CAF proliferative activity (left) and TAM infiltration (right) were quantitatively evaluated by calculating the ratio of vimentin or CD68 antibody positive staining area to the total area in each field, and the mean value from ten fields under 200x microscopy was indicated. *P < 0.05; **P < 0.01; n.s.: not significant.
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fig2: Alterations of tumor microenvironments under different ZHENG conditions. (a) Xenograft tumor models were established as described. On the next day, three types of ZHENG, namely, Shi-Re, Pi-Xu, and Xue-Yu were established. Tumors were obtained 4 wks after implantation. IHC staining for vimentin and α-SMA on sections of tumors was performed for evaluating CAF proliferative activities (top). IHC staining for CD68 was performed for evaluating TAM infiltration (low). Original magnification, 200x. (b) CAF proliferative activity (left) and TAM infiltration (right) were quantitatively evaluated by calculating the ratio of vimentin or CD68 antibody positive staining area to the total area in each field, and the mean value from ten fields under 200x microscopy was indicated. *P < 0.05; **P < 0.01; n.s.: not significant.

Mentions: As it is recognized that in many tumors the stroma is characterized by an increase in fibroblast proliferation, we immunostained CAFs using the fibroblastic marker vimentin combined with the defined myofibroblast marker α-smooth muscle actin (α-SMA) to investigate the proliferative activity of CAF [9]. We found that the number of both vimentin- and α-SMA-positive cells was decreased in tumors from the Shi-Re and Pi-Xu ZHENG models of pancreatic cancer compared with the control tumor, while tumors from the Xue-Yu model exhibited no changes in CAF activity (Figures 2(a) and 2(b)). This observation suggested that CAF proliferative activity in tumors was altered differently on the basis of ZHENG conditions.


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)

Alterations of tumor microenvironments under different ZHENG conditions. (a) Xenograft tumor models were established as described. On the next day, three types of ZHENG, namely, Shi-Re, Pi-Xu, and Xue-Yu were established. Tumors were obtained 4 wks after implantation. IHC staining for vimentin and α-SMA on sections of tumors was performed for evaluating CAF proliferative activities (top). IHC staining for CD68 was performed for evaluating TAM infiltration (low). Original magnification, 200x. (b) CAF proliferative activity (left) and TAM infiltration (right) were quantitatively evaluated by calculating the ratio of vimentin or CD68 antibody positive staining area to the total area in each field, and the mean value from ten fields under 200x microscopy was indicated. *P < 0.05; **P < 0.01; n.s.: not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Alterations of tumor microenvironments under different ZHENG conditions. (a) Xenograft tumor models were established as described. On the next day, three types of ZHENG, namely, Shi-Re, Pi-Xu, and Xue-Yu were established. Tumors were obtained 4 wks after implantation. IHC staining for vimentin and α-SMA on sections of tumors was performed for evaluating CAF proliferative activities (top). IHC staining for CD68 was performed for evaluating TAM infiltration (low). Original magnification, 200x. (b) CAF proliferative activity (left) and TAM infiltration (right) were quantitatively evaluated by calculating the ratio of vimentin or CD68 antibody positive staining area to the total area in each field, and the mean value from ten fields under 200x microscopy was indicated. *P < 0.05; **P < 0.01; n.s.: not significant.
Mentions: As it is recognized that in many tumors the stroma is characterized by an increase in fibroblast proliferation, we immunostained CAFs using the fibroblastic marker vimentin combined with the defined myofibroblast marker α-smooth muscle actin (α-SMA) to investigate the proliferative activity of CAF [9]. We found that the number of both vimentin- and α-SMA-positive cells was decreased in tumors from the Shi-Re and Pi-Xu ZHENG models of pancreatic cancer compared with the control tumor, while tumors from the Xue-Yu model exhibited no changes in CAF activity (Figures 2(a) and 2(b)). This observation suggested that CAF proliferative activity in tumors was altered differently on the basis of ZHENG conditions.

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