Freshly isolated bone marrow cells induce death of various carcinoma cell lines

Abstract

In some carcinomas such as digestive tract carcinomas, bone marrow infiltration by tumor cells is a frequent event but usually remains a micrometastatic disease and rarely induces overt bone lesions. The mechanisms responsible for the control of these metastases in the bone marrow remain poorly known. We show that freshly isolated bone marrow cells from human, murine and rat origin rapidly kill a wide range of syngeneic or xenogeneic carcinoma cell lines in culture. Further analysis of this cytotoxic process in the rat indicated that neither resident bone marrow macrophages nor NK cells were responsible for this cytotoxic effect that was restricted to a subpopulation of bone marrow cells expressing CD90 (Thy-1), a marker of hemopoietic precursors. The tumoricidal activity of these cells did not require longterm culture nor addition of exogenous cytokines or growth factors. A subset of CD90 ؉ cells that rapidly differentiates into CD163(ED2)-expressing macrophages was observed to be responsible for tumor cell killing. These macrophages induced a non-apoptotic death of tumor cells, a process that required both a direct interaction with the tumor cell and nitric oxide (NO) production through the activation of inducible nitric oxide-synthase (iNOS). This ability of pluripotent hemopoietic stem cells to rapidly differentiate into macrophages capable of killing invasive tumor cells may account for the limited expansion of micrometastases of some carcinomas in the bone marrow.

Nitric Oxide and Cancer Development

“…Nearly simultaneous with the discovery that NO was EDRF, independently Hibbs and coworkers showed that NO was the active factor in the macrophage mediated killing of tumor cells in model systems 1 . Research in the area of NO mediated killing of tumor cells by macrophages has continued since the early observations, and as anticipated, observations since then have demonstrated that the processes and cell biology involved is more complex than originally conceived 2 . This area will not be covered in this review.…”

Lymph node micrometastases are associated with disease recurrence and poor survival for early-stage non-small cell lung cancer patients: a meta-analysis

“…Tumor cells that are detected molecularly in the LN of patients with NSCLC are subjected to one of three fates: death, dormancy, or proliferation [18]. Most metastatic cells die in this hostile microenvironment [19,20], or they balance the growth rates with the death rates [21]. Other cells adapt by responding to stimuli from the microenvironment.…”

Human amniotic membrane-derived epithelial stem cells display anticancer activity in BALB/c female nude mice bearing disseminated breast cancer xenografts

“…Indeed, multiple stem cells engineered to express anticancer genes at a specific tumor locus, have been reported to effectively suppress tumors (1,4,11,14,17,(22)(23)(24)(25)(26)(27). However, certain reports have shown that non-engineered native stem cells have an inherent ability to inhibit the growth of several types of cancer cells (28,29). However, the use of engineered stem cells can help solve unexpected problems associated with transfected genes, such as mutation, inappropriate insertion into genomic DNA and viral vector virulence.…”