Influence of bone marrow-derived hematopoietic cells on the tumor response to radiotherapy: experimental models and clinical perspectives - PubMed (original) (raw)

Review

Influence of bone marrow-derived hematopoietic cells on the tumor response to radiotherapy: experimental models and clinical perspectives

G-One Ahn et al. Cell Cycle. 2009.

Abstract

In this review, we highlight some of recent studies underscoring the importance of the tumor microenvironment, especially the role of bone marrow-derived myeloid cells, in restoring tumor growth after irradiation. Myeloid cells are hematopoietic cells that give rise to monocytes and macrophages in the peripheral blood and tissues. These cells have been shown to be proangiogenic in tumors promoting tumor growth. We also discuss our previously unpublished results on the effect of irradiation on the tumor vasculature including pericyte and basement membrane coverage to the endothelium of tumor blood vessels. We summarize the clinical significance of these studies including the use of MMP-9 inhibitors, administering white blood cell boosters, or planning safety margin of tumor volumes, in order to improve overall clinical benefits in cancer patients treated with radiotherapy.

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Figures

Figure 1

Figure 1

(A) Growth of MT1A2 tumor in FVB mice that did not receive whole body radiation (WBR) or bone marrow transplantation (BMT) (open circles) or in FVB mice that receive WBR at 9 Gy followed by BMT from Tie2lacZ transgenic mice (closed circles) 4 weeks prior. Tumors were implanted at the same time and monitored for their growth. (B) RIF tumor growth in female C3H mice that received 9 Gy local irradiation at the tumor implantation site (open circles) or in female C3H mice that received 9 Gy WBR followed by BMT from male C3H mice (closed circles) at the same time as the group in open circles. Tumors were implanted 4 weeks later, irradiated at approximately 200 mm3 with 20 Gy (arrow), and were monitored for their growth. Symbols in (A and B) are the mean ± s.e.m. for n = 5 per group.

Figure 2

Figure 2

(A) Growth of MT1A2 tumors that were non-irradiated (control; open circles), irradiated and re-grown (IR tumor; closed circles), or grown in previously irradiated tissues (pre-IR bed; closed squares) in FVB mice. Arrowhead indicates local irradiation of 20 Gy to the ‘IR tumor group only. Numbers in red indicate points at which tumors were excised and examined histologically for basement membrane (B) and for pericytes (Fig. 3). Reproduced from with permission. (B) Left: Immunostaining of tumors in A for endothelial cells (CD31; red) or basement membrane (type IV collagen, green). Numbers in parentheses correspond to the numbers in red from (A). Right: The number of endothelial cells was subtracted from that of basement membrane to determine the presence of basement membrane empty sleeves (see the text). The difference in means between different volumes or treatment groups did not reach a statistical significance (p > 0.05).

Figure 3

Figure 3

Immunostaining of tumors from Figure 2 for endothelial cells (CD31; red) or pericytes (α-smooth muscle actin; α-SMA; green). Numbers in parentheses are as in Figure 2. Percentage of endothelial cells associated with pericytes were calculated and shown on right. Note that pre-IR tumors showed the percent endothelial cells with pericyte coverage to be significantly lower than other groups (p < 0.001).

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