J Cancer 2015; 6(2):128-138. doi:10.7150/jca.10787
The Quantum of Initial Transformed Cells Potentially Modulates the Type of Local Inflammation Mechanism Elicited by Surrounding Normal Epithelial Tissues and Systemic Immune Pattern for Tumor Arrest or Progression
1. Department of Biotechnology, Dalian Medical University, Dalian 116044, P.R. China.
2. Department of Pathology, Dalian Medical University, Dalian 116044, P.R. China.
3. Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
Owusu L, Wang B, Du Y, Li W, Xin Y. The Quantum of Initial Transformed Cells Potentially Modulates the Type of Local Inflammation Mechanism Elicited by Surrounding Normal Epithelial Tissues and Systemic Immune Pattern for Tumor Arrest or Progression. J Cancer 2015; 6(2):128-138. doi:10.7150/jca.10787. Available from http://www.jcancer.org/v06p0128.htm
The immune/ inflammation system potentially serves to arrest, eliminate or promote tumor development. Nonetheless, factors that dictate the choice are not comprehensively known yet. Using a B16/F1 syngeneic wild type model, we evaluated the essentiality of initial transformed cells' density for overt tumor development, the molecular trends of inflammatory mediators in the normal tumor-adjacent epithelial tissues (NTAT), and how such local events may reflect systematically in the host. Overt tumors developed, within an observatory period of at least 45 days and 90 days at most, only in mice inoculated with cancer cells above a limiting threshold of 1× 103 cells. Immunoblots showed early, intense and transient presence of IL-1β, IFN-γ, and both the all-thiol and disulfide forms of HMGB1 in the NTAT of non-tumor bearing mice. However, all-thiol form of HMGB1 and delayed but aberrant IL-6 expression characterized chronic inflammation in tumor bearing hosts. These local epithelial tissue events uniquely reflected in host's systemic cytokines dynamics where stable Th1/Th2 signature (IFN-γ/ IL-4) coupled with early Th1 cells polarization (IL-12/ IL-4) evidenced in non-tumor hosts but highly fluctuating Th1/ Th2 profile in tumor hosts, even before tumors became overt. This hypothesizes that the physical quantum of transformed cells that may either spontaneously arise or accrue at a locus may be crucial in orchestrating the mechanism for the type of local epithelial tissue and systemic immune/ inflammatory responses essential for tumor progression or arrest.
Keywords: Cancer cell density, minimum tumorigenic threshold, inflammation, overt tumor, Th1/Th2/Th17 cytokines.