Table 1.
Factors of primary soil-to-seed signaling events involved in cancer metastasis
| Stroma cell type | Molecules | Underlying mechanisms | Cancer type | Ref |
|---|---|---|---|---|
| TAMs | miR-223 | Regulates the invasiveness of cancer cells through exosome-mediated delivery of oncogenic miRNAs. | Breast cancer | [89] |
| CCL18 | Promotes the invasiveness of cancer cells by triggering integrin clustering and enhancing their adherence to extracellular matrix. | Breast cancer | [90] | |
| CCL20 | CCL20 secreted by TAMs enhances the invasive properties of cancer cells via its unique receptor CCR6. | Pancreatic cancer | [91] | |
| Lcn2 | TAM-derived Lcn2 promotes cancer cell dissemination by inducing EMT and resulting in increased cancer cell motility and invasion. | Breast cancer | [92] | |
| MSCs | CCL5/ CCR9 |
MSC-derived chemokines act on cancer cells to enhance their motility, invasion and metastasis. | Breast cancer | [93, 94] |
| DDR2 | MSC-derived DDR2 in the primary tumor endows cancer cells with growth and migratory advantage through alignment with collagen. | Breast cancer | [95] | |
| ECs | PHD2 | Haplodeficiency of PHD2 normalizes the endothelial lining and vessel maturation, resulting in inhibited metastasis. | Melanoma Lung cancer Pancreatic cancer |
[96] |
| IL6 | EC-derived IL-6 triggers the increased invasion of cancer cell. | Prostate cancer | [97] | |
| Undetermined | EC-bound tumor cells show a significantly higher anoikis resistance via the activation of Src-FAK pathway. | Squamous carcinoma | [98] | |
| CAFs | SDF-1/CXCL12 | Promote tumor growth and angiogenesis through their ability to secrete stromal cell-derived factor 1 (SDF-1). | Breast cancer | [99] |
| Cav1 | Stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. | Breast cancer | [100] | |
| Exosomes | Fibroblast-secreted exosomes promote breast cancer cell protrusive activity and motility via Wnt-planar cell polarity (PCP) signaling. | Breast cancer | [101] | |
| Adipocytes | Undetermined | Adipocytes promote tumor cell invasion and EMT program. | Melanoma | [105] |
| Undetermined | Pre-adipocytes increase prostate cancer metastasis via modulation of signaling pathways. | Prostate cancer | [106] | |
| IGFBP-2 | Adipocytes stimulate invasion of cancer cells by secreting IGFBP-2. | Breast cancer | [107] |