Rejection of intradermally injected syngeneic tumor cells from mice by specific elimination of tumor-associated macrophages with liposome-encapsulated dichloromethylene diphosphonate, followed by induction of CD11b+/CCR3−/Gr-1− cells cytotoxic against the tumor cells

Abstract

Tumor cell expansion relies on nutrient supply, and oxygen limitation is central in controlling neovascularization and tumor spread. Monocytes infiltrate into tumors from the circulation along defined chemotactic gradients, differentiate into tumor-associated macrophages (TAMs), and then accumulate in the hypoxic areas. Elevated TAM density in some regions or overall TAM numbers are correlated with increased tumor angiogenesis and a reduced host survival in the case of various types of tumors. To evaluate the role of TAMs in tumor growth, we here specifically eliminated TAMs by in vivo application of dichloromethylene diphosphonate (DMDP)-containing liposomes to mice bearing various types of tumors (e.g., B16 melanoma, KLN205 squamous cell carcinoma, and 3LL Lewis lung cancer), all of which grew in the dermis of syngeneic mouse skin. When DMDP-liposomes were injected into four spots to surround the tumor on day 0 or 5 after tumor injection and every third day thereafter, both the induction of TAMs and the tumor growth were suppressed in a dose-dependent and injection number-dependent manner; and unexpectedly, the tumor cells were rejected by 12 injections of three times-diluted DMDP-liposomes. The absence of TAMs in turn induced the invasion of inflammatory cells into or around the tumors; and the major population of effector cells cytotoxic against the target tumor cells were CD11b(+) monocytic macrophages, but not CCR3(+) eosinophils or Gr-1(+) neutrophils. These results indicate that both the absence of TAMs and invasion of CD11b(+) monocytic macrophages resulted in the tumor rejection.

Fragmented Sleep Accelerates Tumor Growth and Progression through Recruitment of Tumor-Associated Macrophages and TLR4 Signaling

“…Indeed, the effects of alterations in TAM polarity and in innate immunity on tumor biological properties including growth trajectory and invasiveness to adjacent tissues have been extensively explored, and our current findings concur with such putative functions. (38-41) As indicated, the number of TAM was markedly increased in SF-exposed mice, and the differences were heterotopically distributed, with tumors from SF-exposed mice displaying preferential M2-type TAM localization in peripheral regions of the tumor. In contrast, SC-derived tumors had increased M1-type TAM, and these were located, in their greatest proportion within the core of the tumor.…”

Individual variation and intraclass correlation in arachidonic acid and eicosapentaenoic acid in chicken muscle

“…Prostaglandin E 2 (PGE 2 ), which is abundantly produced in such tumors [52], stimulates tumor angiogenesis [52], i.e . the ingrowth of blood vessels in the tumor [52,53], which will in turn reduce oxygen and nutrient limitation [54] of the rate of tumor growth, thus leading to faster progression of the disease. PGE 2 also inhibits NK cells [55], lymphokine-activated killer (LAK) cells [56] and cytotoxic CD8 + cells [57], which all are important in anti-tumor immunological defense [55,58,59], at the same time as prostaglandin overproduction in the tumor also must be expected to increase pain associated with cancer.…”

Dasatinib alters the metastatic phenotype of B16-OVA melanoma in vivo

“…This model is clinically relevant because B16F10 was derived from a spontaneously forming melanoma which, like its human counterparts, is poorly immunogenic and expresses no MHC class II and little MHC class I. 27 Notwithstanding this lack of immunogenicity, the involvement of regulatory T cells (Tregs), 28 CD8 + T cells, 29 tumor associated macrophages (TAMs), 30 and natural killer (NK) cells 29 in B16F10 tumor-bearing mice has been documented. Therefore, the rationale for investigating the in vivo effects of dasatinib in this model is based upon the known activity of SFK's in these host cell types and by the correlation of increased Src expression with increased metastatic capacity of B16F10 tumor cells.…”