Table 2.

Experimental versus spontaneous metastasis assays in cancer therapeutics^*

	Experimental metastasis	Spontaneous metastasis
Advantages	Controlled number of cells delivered Short time for evidence of metastatic disease Cell lines available for various tumour types (syngeneic and xenograft) Metastatic disease can be targeted to specific sites	Metastatic spread follows natural route and mechanisms Examination of all steps in metastatic cascade Minimal number of passages used to isolate highly metastatic cells Closely resembles clinical disease (spread and manifestation)
Disadvantages	Primarily generates metastases in one tissue (e.g. lung metastases from tail vein injection of tumour cells) Cell lines isolated through multiple passages to enhance tissue-specific ability Artificial route of delivery Examination limited to post-extravasation step	Longer time needed for metastatic disease to become evident Limited number of models (syngeneic and xenograft) Metastatic disease not confined to one location Asynchronous development of metastatic disease
Examples of use in experimental therapeutics	Human MDA-MB231(231-BR1) breast cancer (i.c.) treated with Vorinostat63 Human MDA-MB-231 breast cancer (i.c.) bone metastases treated with an inhibitor of HIF1α combined with a TGFβ inhibitor69 Human MDA-MB231(231-BR1) breast cancer (i.c.) treated with Lapatinib54 Human HM7 colorectal carcinoma (i.s.) treated with VEGF-specific antibody55 Murine CT26 colon carcinoma (i.s. and i.v.) treated with 5-Fluorouracil1 Murine B16 melanoma (i.v.) treated with VEGFR2-specific antibody and metronomic CTX36	Human MDA-MB231(ERBB2+) breast cancer treated with CTX and trastuzumab46 Human LM2-4 breast cancer treated with metronomic CTX and UFT34 Human 113/6-4L melanoma treated with metronomic CTX and vinblastine35 Human LSLiM6 human colon carcinoma treated with modified citrus pectin30 Murine B16 melanoma treated with VEGFR1-specific antibody29 Murine Lewis Lung carcinoma treated with TNP-470 alone, or combined with chemotherapy31 Murine EMT-6 breast carcinoma treated with alkylating agents32

CTX, cyclophosphamide; HIF1α, hypoxia-inducible factor 1\g=a\; i.c., intracardiac injection; i.s., intrasplenic injection; i.v., intravenous injection; TGFβ, transforming growth factor-β; VEGF, vascular endothelial growth factor; VEFGR, VEGF receptor.

^*Additional examples of spontaneous and experimental metastasis assays in cancer therapeutics were recently reviewed by Steeg and Theodorescu (REF. 68).