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Table 1 Factors of primary soil-to-seed signaling events involved in cancer metastasis

From: Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis

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]