Table 1.

Clinical studies of adipose tissue and tumor crosstalk

Author (year, journal)Study population/tissue typeFocusResults
Breast cancer
Mullooly et al (2017, Breast Cancer Res; ref. 75)
  • Postmenopausal women (n = 83)

  • Benign breast tissue

  • Crown-like structures and sex steroid hormones in breast adipose tissue

  • Crown-like structures were observed in 36% of the tissue samples and increased in obese patients (P = 0.03)

  • Crown-like structures were not related to hormone levels or tumor characteristics, but were associated with hormone ratios

Koru-Sengul et al (2016, Brest Cancer Res Treat; ref. 78)
  • Women (n = 150)

  • Caucasian (CA), non-black Latinas (NBLA), blacks (BL); each

  • Breast tissue

  • Association between the number of TAM and/or crown-like structures with patient survival

  • Differences among ethnicities (Caucasian, non-black Latinas, blacks)

  • Significantly different density of TAMs among ethnicities, with black patients having the highest, followed by non-black Latinas, and Caucasian presenting the lowest density.

  • The majority of TAMs presented an immunosuppressive, with black patients showing the highest density

Jung et al (2015, Tumour Biol; ref. 76)
  • Women (n = 939)

  • n = 642 fibrous stroma type (100% fibrous stroma)

  • n = 297 adipose stroma (>50% adipose tissue in tumor)

  • Breast tissue

  • Relationship between stroma type and tumor phenotype classification

  • Effect of stroma type on gene expression of tumor cell

  • Luminal A subtype was more prevalent in adipose stroma breast cancer type (P < 0.001)

  • Tumor cell expression of podoplanin and FAPα was higher in adipose stroma type, while higher expression of prolyl 4-hydroxylase and PDGFRα in fibrous stroma type

Iyengar et al (2015, Clin Cancer Res; ref. 66)
  • Women (n = 227)

  • Cohort 1: cross-sectional prospective study (n = 100) who undergo mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90)

  • Cohort 2: retrospective study (n = 127) who developed metastatic cancer

  • Breast WAT

  • Breast WAT inflammation

  • Circulating inflammatory factors

  • Breast WAT inflammation was detected in 52 of 100 patients (52%) of cohort 1 and 52 of 127 patients (41%) of cohort 2

Iyengar et al (2015, Cancer Prev Res; ref. 77)
  • Women (n = 237)

  • Breast WAT

  • Association of breast WAT inflammation with BMI and menopause

  • WAT inflammation was significantly associated with menopausal status (P < 0.001) and BMI (P < 0.001)

Savolainen-Peltonen et al (2014, J Clin Endocrinol metab; ref. 70)
  • Postmenopausal women (n = 14) with ER-positive breast tumor

  • Women undergoing breast reduction mammoplasty (n = 14)

  • Breast subcutaneous adipose tissue

  • Estrone, estradiol, and estradiol fatty acyl ester concentrations in breast adipose tissue

  • mRNA expression levels of estrogen-converting enzymes in breast adipose tissue

  • Estradiol concentration in breast subcutaneous adipose tissue was lower in women with cancer compared with controls (P = 0.002), whereas the serum concentrations did not differ

  • mRNA expression for 17β-hydroxysteroid dehydrogenase type 12 was lower in cancer patients (P = 0.018)

Morris et al (2011, Cancer Prev Res; ref. 68)
  • Obese (BMI ≥ 30 kg/m2) women (n = 30)

  • Breast adipose tissue

  • Aromatase activity

  • Adipocyte size

  • Serum inflammation marker

  • The severity of breast inflammation, defined as the CLS (crown-like structures)-B index, correlated with both BMI (P < 0.001) and adipocyte size (P = 0.01)

  • Increased NF-κB binding activity and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women

Colorectal cancer
Liesenfeld et al (2015, Am J Clin Nutr; ref. 8)
  • Women or men (n = 59)

  • VAT and SAT

  • VAT and SAT: 1,065 metabolites

  • Serum: 1,810 metabolites

  • Anthropometric measurements

  • VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis–related enzymes (PTGD/PTGS2S)

  • Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT

  • Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides

  • Logistic regression identified lipids in patients' adipose tissues, which were associated with tumor stage

Amor et al (2015, Int J Colorectal Dis; ref. 73)
  • Women or men (n = 36)

  • Visceral peritumoral and nontumoral adipose tissue

  • Differences between obese and lean patients' adipose tissue secretion

  • Peritumoral adipose tissue secreted higher amounts of nitrites and nitrates than nontumoral

  • Peritumoral adipose tissue secretion was increased in obese cancer patients

Notarnicola et al (2012, Lipids; ref. 64)
  • Women or men (n = 32)

  • Adipose tissue (10 cm distance from tumor location)

  • Enzymes (LPL and FAS) activity and gene expression

  • Significant reduction in both LPL and FAS gene expression and activity levels in adipose tissue adjacent to tumor lesion compared with those detected in paired tissue distant from the cancer

Catalan et al (2011, J Nutr Biochem; ref. 71)
  • Women or men with colorectal cancer (n = 11)

  • Healthy women or men (n = 18)

  • VAT

  • mRNA levels of proinflammatory adipokines (lipocalin-2, chitinase-3 like-1 and osteopontin, IGF1, IGFBP3) and angiogenic-related factors (HIF-1, VAGF, and MMP2 and MMP9) in VAT

  • Increased mRNA expression levels of lipocalin-2 (P = 0.014), osteopontin (P = 0.027), TNFα (P = 0.016), and chitinase-3 like-1 (P = 0.006) in patients with colorectal cancer

  • Significantly higher levels of HIF-1, VAGF, and MMP2 (P < 0.001) in patients with colorectal cancer

  • Expression of IGF-1, IGFBP3, and MMP9 followed same, but not significant (P > 0.001)

Esophageal cancer
Trevellin et al (2015, Oncotarget; ref. 65)
  • Women or men (n = 60)

  • Peritumoral and distal adipose tissue of esophageal cancer patients

  • Peritumoral adipose tissue: adipocyte and adipokine expression

  • BMI and obesity-related parameters (e.g., leptin mRNA levels)

  • Increased adipocyte size was directly associated with leptin expression, angiogenesis (CD31), and lymph angiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients

Lysaght et al (2011, Br J Surg; ref. 79)
  • Women or men (n = 35)

  • Omental adipose tissue

  • T-cell activation status and cytokine production in omental adipose tissue

  • Omental CD4+ and CD8+ T cells displayed significantly enhanced expression of the T-cell activation markers CD69 (P < 0.001) and CD107a (CD8+ T cells: P < 0.01), and significantly decreased CD62L expression (P < 0.05), compared with blood

  • IFNγ was the most abundant cytokine expressed by omental T cells

Colorectal and esophageal cancer
Lysaght et al (2011, Br J Surg; ref. 79)
  • Women or men (n = 35)

  • SAT and VAT of colorectal or esophageal patients

  • Effect of SAT or VAT conditioned media on colorectal or esophageal cancer cells

  • Levels of proinflammatory and tumor proliferative properties in VAT and SAT

  • Significantly higher levels of VEGF and IL6, and higher proportions of CD8 T cells and NKT cells in VAT

  • Cancer cells cultured with VAT conditioned media showed significant increase in cell proliferation

Endometrial cancer
Modesitt et al (2012 Int J Gynaecol Cancer; ref. 72)
  • Women (n = 8)

  • with endometrial cancer (n = 4)

  • without endometrial cancer (n = 4)

  • VAT, SAT, and endometrium

  • Gene expression in VAT and SAT

  • n = 19 gene sets were regulated in in VAT and SAT

  • n = 47 gene set pathways in in VAT

  • n = 38 gene set pathways in SAT

  • n = 5 pathways were significantly regulated in all three tissues, including glycolysis/ribosome, peroxisome proliferator activator receptor signaling, pathogenic Escherichia coli infection, and natural killer–mediated cytotoxicity

Prostate cancer
Zhang et al (2016, Cytokine; ref. 82)
  • Women or men (n = 30)

  • Periprostatic adipose tissue

  • Gene expression of IL6, leptin, and adiponectin in per-prostatic adipose tissue

  • IL6 and leptin were positively associated with the aggressiveness of prostate cancer, whether adiponectin was negatively associated

Venkatasubramanian et al (2014, Prostate; ref. 81)
  • Men (n = 40)

  • Periprostatic adipose tissue and SAT

  • Levels of secretes in periprostatic adipose tissue

  • Periprostatic adipose tissue secretions were significantly more proliferative in both prostate cancer cells and endothelial cells compared with lean or overweight men and SAT

Ribeiro et al (2012, BMC Med; ref. 69)
  • Men (n = 18)

  • Periprostatic adipose tissue

  • Gene expression in human periprostatic adipose tissue

  • In obese and overweight patient samples increased expression of proliferative, adipogenic, and immunoinflammatory genes (e.g., LEP and ANGPT1)

Finley et al (2009, J Urology; ref. 74)
  • Men (n = 7)

  • Periprostatic adipose tissue

  • Cytokine expression in periprostatic adipose tissue

  • Inflammatory infiltrates in periprostatic adipose tissue

  • IL6 in periprostatic adipose tissue conditioned medium was about 375 times greater compared with patients' serum

  • Periprostatic adipose tissue showed a greater phosphorylation on STAT3 with high-grade tumors.

ENT cancer
Iyengar et al (2016, Cancer; ref. 83)
  • Women or men (n = 125)

  • Tongue and neck tissue

  • Association between WAT inflammation and cancer-specific survival

  • WAT inflammation was associated with BMI, increased tumor thickness, and vascular invasion (P < 0.05)

  • WAT inflammation was associated with worse cancer-specific and overall survival in early-stage cancer patients

  • Abbreviations: CLS, crown-like-structures, FAS, fatty acid synthase; FERKO, fat-specific ERα knockout mouse; Lcn2, lipocalin 2; LPL; lipoprotein lipase; Ob-R, leptin receptor; PDGFRα, platelet-derived growth factor receptor α; PLA2G10, phospholipase A2 G10; PTGD/PTGS2S, prostaglandin synthesis–related enzymes; TAM, tumor-associated macrophages.