Table 1.

Experimental observations and clinical relevance of the listed features in pancreatic cancer.

Feature	Experimental Observations	Clinical Relevance
ALDH1	Mediates resistance against chemo(radio-)therapy [13,14,15] Enrichment of ALDH1+ PCCs following gemcitabine treatment [16]	Correlates with poor survival [15,17] Low expression correlates with poor survival [18]
αSMA	Correlation with aligned collagen [19]	Correlates with survival [20,21]
CAV1	Modulates response to substrate stiffness and stromal remodeling [22,23] Promotes PCC proliferation, invasion, treatment resistance [24,25]	High expression in PCCs correlates with larger tumor size, higher differentiation grade, worse outcome [25,26] Loss of stromal expression correlates with stage [27]
CD44	Confers CSC phenotype Interaction with HA promotes PCC migration, MMP14-upregulation [28], resistance to gemcitabine [29,30], metastatic potential [31,32]	Correlates with early recurrence, poor survival, advanced stage, lower grade [30,33,34,35,36,37,38]; no correlation with survival, advanced stage, differentiation grade [39,40] Increase of CD44 + PCCs after gemcitabine treatment [41,42]
CD133	Induces stemness [43], EMT [44,45,46], altered metabolic profile and chemoresistance [44,47]	Correlates with metastasis and survival [40,48,49] No correlation with survival, stage, differentiation grade [39,40,50] Numerous CD133+ PCCs after gemcitabine treatment correlates with poor outcome [42,51]
Col I	Promotes proliferation, migration and metastasis [52,53,54,55,56,57,58,59] Reduces sensitivity to gemcitabine and 5-FU [54,58] Alignment enhances migration, invasive velocity and directionality [60,61,62]	High content correlates with poor survival [63], with longer survival [64] High alignment correlates with poorer survival independent of traditional prognostic determinants [65]
Col III	Promotes proliferation and migration [66]	Pretreatment serum levels correlate with survival [67,68]
FN	Affects resistance to chemotherapy [69]	Correlates with higher stage, poorer survival [70,71] No correlation with survival [72,73]
HA	Increases interstitial pressure and influences drug delivery [60,74,75,76,77] Promotes PCC proliferation, motility and metastasis via binding to CD44 [78,79,80,81]	Correlates with rapid tumor progression [82] and survival [63,83]; no correlation with survival [33,82] Treatment with recombinant hyaluronidase and gemcitabine prolongs survival in patients with HA-rich tumors [84]
ITGα2β1	Mediates collagen I-induced proliferation and migration of PCCs [59,85] ITGβ1-blocking inhibits invasiveness of PCCs [62]	Overexpression correlates with poorer overall and disease-free survival, higher grade and stage [86]
ITGα5β1	Mediates PCC migration along fibronectin and increased PCC survival [87,88]	Overexpression of ITGα5 correlates with poorer overall survival [21]
MMP14	Enables PCC migration and release of growth factors, incl. TGFβ [89,90] Sheds cell-surface biomolecules, incl. CD44 [91] Upregulation sensitizes to gemcitabine [92,93]	Enhanced expression in metastasis compared to primary PC [94,95]

ALDH1, aldehyde dehydrogenase 1; αSMA, α-smooth muscle actin; CAV1, caveolin-1; Col, collagen; CSC, cancer stem cell; EMT, epithelial-mesenchymal transition; FN, fibronectin; HA, hyaluronan; ITG, integrin; MMP14, matrix metalloproteinase 14; PCC, pancreatic cancer cell; TGFβ, transforming growth factor β; 5FU, fluorouracil.