Recently, Professor Song Erwei from the Department of Breast Medical Oncology of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University released his six-year team study and declared that breast cancer cells can activate M2 macrophages cells in the tumor microenvironment and cause further “epithelial - mesenchymal transition”, thus leading to metastasis of breast cancer cells.
What is the leading cause for the enlargement and metastasis of malignant tumor? As early as a century ago, British surgeon Stephen Paget presented his famous “seed and soil” theory of metastatic dissemination: “the processes of metastasis did not occur by chance but rather, for the ‘seed’ (cancer cells) to take root, you need the right ‘soil’ (tumor microenvironment).” For malignant tumor, does the "seed” in turn affect its "soil”, and create a vicious cycle to promote tumor metastasis? Recently, Professor Song Erwei from the Department of Breast Medical Oncology of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University released his six-year team research report and declared that breast cancer cells can activate M2 macrophages cells in the tumor microenvironment and cause further “epithelial - mesenchymal transition ", thus leading to metastasis of breast cancer cells. According to the 39 health network, this study has been officially published in the Cancer Cell, a well-known international journal of Oncology on May 12, 2014.
Distant metastasis of tumor is the leading cause of death for breast cancer
Breast cancer accounts for the highest morbidity for women over the world in all the malignancies. According to statistics, one woman is diagnosed with breast cancer every three minutes. China has a growth rate of 3-4% per annum in the incidence of female breast cancer, which is well above the world’s average growth rate. Professor Liu Qiang, deputy director of the Department of Breast Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University published the “Chinese breast disease investigation report” in 2010. The report had already shown a 38.91% increase in the death rate of the urban breast cancer patients between 2003 and 2009. Breast cancer has indeed become one of the biggest threats to women's health. Distant metastasis of tumor is the leading cause of death for breast cancer. For example, triple negative breast cancer (TNBC) has higher level of malignancy. 70% of distant metastasis occur in brain and lungs. This leads to difficulties in applying suitable treatment. Professor Liu said: “Even for the early-stage breast cancer patients, there is still 30-40% possibility for relapse and distant metastasis after surgery. Ways to prevent? Early diagnosis on predicting the level of risk of distant metastasis for breast cancer patients has become a problem that must be addressed in breast cancer studies.”
“Epithelial - mesenchymal transition” becomes the critical step for breast cancer cells metastasis
“Tumor cells are epithelial cells, which are normally “immobile”. However, if the “epithelial - mesenchymal transition” occurs, the epithelial cells would transform into fibroblast-like cells, which enhance migration and invasion as well as contribute to tumor metastasis within the tumor microenvironment,” answered by Professor Song Erwei, the article’s main author. “What are the causes for epithelial - mesenchymal transition of tumor cells? In addition to the genetic changes, macrophages around the tumor cells are undoubtedly the biggest "accomplice".”
A study that was done few years ago reported that tumor cells with epithelial - mesenchymal transition and tumor-associated macrophages are both located in the forefront of the tumor, suggesting that there is interaction between the two. However, animal experiments have found that macrophages in human body had huge differences compared with the ones in mice’s body. The homologous protein, which was found in mice’s body, was not discovered in human’s tumor-associated macrophages. “The use of animal model has become a bottleneck for the study in the tumor microenvironment,” claimed by Professor Shen Huiyong, Director of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. In 2008, the study team led by Song Erwei transplanted human hematopoietic stem cells in the body of an immunodeficient mice after radiation. Human tumor cells were then injected into the mice’s breast in order to establish human tumor-like “humanized mouse tumor models”, which revealed the specific relationship between tumor cells with epithelial - mesenchymal transition and tumor-associated macrophages.
Reciprocal causation between cancer and chronic inflammation promotes a vicious cycle for breast cancer metastasis
“There is a large number of inflammatory cells in the tumor 'soil' (tumor microenvironment), in which macrophages are ones that are the most commonly found. Macrophages are divided into two main types: M1 macrophages and M2 macrophages. M1 macrophages can kill tumor cells, while M2 macrophages can help the growth and metastasis of tumor cells,” Professor Liu Jiang explained. Due to the fact that a small fraction of breast cancer cells have epithelial - mesenchymal transition, secretion of cytokines GM-CSF and tumor metabolism of lactic acid induce macrophages to differentiate into M2. M2 macrophages can then secrete chemokine’s CCL18 to induce epithelial - mesenchymal transition of breast cancer cells and secretion of cytokines GM-CSF, eventually forming a vicious cycle.
Early diagnosis on predicting the level of risk of distant metastasis for breast cancer patients provide new targets for the treatment of triple negative breast cancer (TNBC)
“With microscope, we discovered that patients with CCL18-positive M2 macrophages (over 20 per field) in breast cancer or high GM-CSF in tumor cells have a higher risk of getting distant metastasis after surgery.” Sun Yat-Sen Memorial Hospital’s Oncology physician Dr. Su Shicheng said. “We can therefore carry out early diagnosis in detecting a patient's level of GM-CSF and CCL18 before surgery to help predict the possibility of having distant metastasis after surgery, as well as designing suitable treatment for the patient.”
