Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, Le QT, Giaccia AJ. Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche. Cancer Cell. 2009 Jan;15(1):35–44.
Abstract
Tumor cell metastasis is facilitated by ‘‘premetastatic niches’’ formed in destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase (LOX) is critical for premetastatic niche formation. LOX secreted by hypoxic breast tumor cells accumulates at premetastatic sites, crosslinks collagen IV in the basement membrane, and is essential for CD11b+ myeloid cell recruitment. CD11b+ cells adhere to crosslinked collagen IV and produce matrix metalloproteinase-2, which cleaves collagen, enhancing the invasion and recruitment of BMDCs and metastasizing tumor cells. LOX inhibition prevents CD11b+ cell recruitment andmetastatic growth. CD11b+ cells and LOX also colocalize in biopsies of human metastases. Our findings demonstrate a critical role for LOX in premetastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease.[/toggle_content]
[custom_table]
| Clodronate Concentration | Total Lipid Concentration | Lipid Composition | Lipid Mole % | Liposome Type | Control Liposomes |
|---|---|---|---|---|---|
| 5 mg/ml | 23.4 mg/ml | EPC/Chol | 84/16 | MLV | none |
| Animal Description | Clodronate Dose | Dosing Method/Site | Target Phagocytes | Local Dosing? | Local Results |
|---|---|---|---|---|---|
| Nude mice | not specified | not specified | CD11b+ bone marrow derived cells | no | N/A |
Notes
- Liposome prep method cited — van Rooijen N, Sanders A. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. Journal of Immunological Methods. 1994 Sep 14;174(1–2):83–93; van Rooijen N, van Kesteren-Hendrikx E. In vivo “depletion of macrophages by liposome-mediated”suicide. Methods in Enzymology [Internet]. 2003 [cited 2012 Feb 25]. p. 3–16.
- No details provided on route of administration, volume or amount dosed or time post-treatment at which depletion was evaluated.
Results
- The authors report that depletion of CD11b+ bone marrow-derived cells reduce those cells present in two mouse tumor models as well as the number and size of metastatic foci found in these models.
- The authors further acknowledge that clodronate liposome depletion is not specific to CD11b+ cells and that the effects of depletion may reduce metastatic tumor size and number by mechanisms not related to CD11b+ cell depletion.